Virginia Foundation for Healthy Youth Publication Database

133 Publications Available

PublicationYear PublicationTitle Authors PublicationJournal PublicationVolume PublicationPage PublicationAbstract PublicationUniversity PublicationLinkPubmed
2008 Characterizing early cigarette use episodes in novice smokers. Addictive Behaviors Acosta , M.C.,Eissenberg , T.,Nichter , M.,Balster , R.L., , Tobacco Etiology Research Network (TERN) Addictive Behaviors 33 106-121 Retrospective self-report data indicate that early cigarette use episodes may be important predictors of smoking. Unfortunately, recall of early experiences are confounded with current smoking. The current study is the first to examine early cigarette use episodes (EUEs) prospectively in novice smokers (less than 15 lifetime cigarettes). Smoking amount, context and subjective experiences for up to five of the first cigarette episodes during their first year of college were collected using weekly internet-based questionnaires and structured interviews. Data were obtained on 538 EUEs from 163 students. EUEs generally occurred within a social/party context; over 90% of EUEs occurred when participants were with other people who were smoking and over 65% occurred while participants were drinking alcohol. Subjective effects across episodes were reported as generally mild and factor analysis yielded Positive, Negative and Sensory/Peripheral effects scales. Subjective effects were related to the amount smoked and inhalation, whereas EUE context, including alcohol use and social context, was not. This study demonstrates that it is possible to study EUEs in college students within days or weeks of their occurrence and that most of these occur in social settings with the concurrent use of alcohol. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/17913378
2015 Effects of menthol on nicotine pharmacokinetic, pharmacology and dependence in mice Alsharari , S.D.,King , J.R.,Nordman , J.C.,Muldoon , P.P.,Jackson , A.,Zhu , A.Z.,Tyndale , R.F.,Kabbani , N.,Damaj , M.I. PLoS One 10(9) e0137070 Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia) and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease) and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c.) for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of α4 and β2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in β2 and α4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of β2 and α4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/26355604
2013a Menthol binding and inhibition of a α7-nicotinic acetylcholine receptors Ashoor , A.,Nordman , J.C.,Veltri , D.,Yang , K.S.,Al Kury , L.,Shuba , Y.,Mahgoub , M.,Howarth , F.C.,Sadek , B.,Shehu , A.,Kabbani , N.,Oz , M. PLoS One 8(7) e67674 Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+)-dependent Cl(-) channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing Ba(2+). Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125)I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+) transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner. https://www.ncbi.nlm.nih.gov/pubmed/23935840
2013b Menthol inhibits 5-HT3 receptor-mediated current Ashoor , A.,Nordman , J.C.,Veltri , D.,Yang , K.S.,Shuba , Y.,Al Kury , L.,Sadek , B.,Howarth , F.C.,Shehu , A.,Kabbani , N.,Oz , M. Journal of Pharmacology and Experimental Therapeutics 347(2) 398-409 The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT3) receptors expressed in Xenopus laevis oocytes. 5-HT (1 μM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC50 = 163 μM) manner. The effects of menthol developed gradually, reaching a steady-state level within 10-15 minutes and did not involve G-proteins, since GTPγS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (-), (+), and racemic menthol inhibited 5-HT3 receptor-mediated currents to the same extent. Menthol inhibition was not altered by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by increasing concentrations of 5-HT. Furthermore, specific binding of the 5-HT3 antagonist [(3)H]GR65630 was not altered in the presence of menthol (up to 1 mM), indicating that menthol acts as a noncompetitive antagonist of the 5-HT3 receptor. Finally, 5-HT3 receptor-mediated currents in acutely dissociated nodose ganglion neurons were also inhibited by menthol (100 μM). These data demonstrate that menthol, at pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT3 receptors. https://www.ncbi.nlm.nih.gov/pubmed/23965380
2008 Rural adolescent attitudes toward smoking and weight loss: relationship to smoking status Bean , M.K.,Mitchell , K.S.,Speizer , I.S.,Wilson , D.B.,Smith , B.N.,Fries , E.A. Nicotine & Tobacco Research 10(2) 279-286 Perceptions that smoking contributes to weight loss are widespread among youth. We examined the association between weight loss and smoking to determine whether supportive attitudes were associated with smoking status and whether this is a particular problem in rural areas. High school students (N=730) completed a survey assessing smoking-related characteristics and behaviors. Attitudes assessed included perceptions of whether weight concerns were the reasons others smoke and personal beliefs about tobacco's effect on weight gain. Smoking status was categorized as never (44%), experimental (42%), and current (14%). Multinomial logistic regressions investigated relationships between attitudes and smoking, adjusting for weight goals, gender, ethnicity, parent/peer smoking, and body mass index. Both attitudinal measures were associated with smoking (p< .05). Nonsmokers and experimental smokers were more likely than current smokers to believe that people smoke to lose weight. Although current smokers were less likely to report that others smoke for weight control, they believed they would gain weight if they quit. Conversely, nonsmokers and experimental smokers were less likely to believe they would gain weight if they do not smoke compared with current smokers. Thus personal attitudes differ from attitudes toward others with respect to weight loss and smoking. Moreover, endorsement of these attitudes can reliably distinguish current versus experimental smokers and may help better clarify the transition to current smoker. Because weight concerns are a significant factor in youth smoking, these issues should be included in intervention efforts, particularly in rural communities where smoking rates are higher and age at initiation is earlier. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/18236292
2010 Stress and tobacco use among African-American Adolescents: the buffering effect of cultural factors Belgrave , F.Z.,Johnson , J.,Nguyen , A.,Hood , K.,Tademy , R.,Clark , T.,Nasim , A. Journal of Drug Education 40(2) 173-88 Tobacco is a leading contributor to morbidity and mortality and a primary reason for health disparities among African Americans. In this study we explore the role of stress in smoking and cultural factors that protect against stress among African-American adolescents. Our sample consisted of 239 youth who were recruited into the study while enrolled in 8th and 12th grade. Measures of risk factors (stress, school transition stress, and community disorganization), moderator or protective factors (religious support and intergenerational connections), and 30-day tobacco use were collected. Hierarchical multiple regression analyses were conducted. Intergenerational connections moderated the effect of stress on past 30-day tobacco use. Religious support moderated the effect of neighborhood disorganization on past 30-day tobacco use. Religious support also moderated the effect of stress on past 30-day tobacco use. The findings have implications for prevention efforts to consider religious beliefs and practices and also to link youth with supportive adults in their community. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/21133330
2008 Continuous nicotine administration produces selective, age-dependent structural alteration of pyramidal neurons from prelimbic cortex. Bergstrom , H.C.,McDonald , C.G.,French , H.T.,Smith , R.F. Synapse 62(31) 31-39 Emerging evidence indicates that adolescence represents a developmental window of enhanced nicotine-induced neuroplasticity in rat forebrain. However, whether nicotine produces age-dependent structural alteration of neurons from medial prefrontal cortex remains to be determined. We characterized the dendritic morphology of layer V pyramidal neurons from prelimbic cortex following adolescent (P29-43) or adult (P80-94) nicotine pretreatment. Nicotine administration was via osmotic pump [initial dose 2.0 mg/(kg day), free base]. Five weeks after drug administration concluded, brains were processed for Golgi-Cox staining and pyramidal neurons digitally reconstructed for morphometric analysis. Overall, nicotine pretreatment produced increased basilar, but not apical, dendritic length of pyramidal cells, a finding consistent with previous work using adult animals. Given the compelling evidence for morphologically distinct functional subtypes of cortical pyramidal neurons, we endeavored to determine whether nicotine-induced dendritic alteration was specific to putative structural subtypes. Neurons were segregated into two groups based on the extent of dendritic arbor at the distal portion of the apical tree (i.e., the apical tuft). The size of the apical tuft was quantitatively determined using principal component analysis. Cells with small and elaborate apical tufts were classified as simple and complex, respectively. We found that adult nicotine pretreatment produced increased basilar dendritic length and branch number in simple but not complex pyramidal cells. In contrast, adolescent nicotine pretreatment produced a modest but significant increase in basilar dendritic length in complex but not simple cells. These data suggest that nicotine alters dendritic morphology of specific subpopulations of pyramidal neurons and that the subpopulation affected is dependent on the age of drug exposure. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/17957736
2010 Chronic nicotine exposure produces lateralized, age-dependent dendritic remodeling in the rodent basolateral amygdala. Bergstrom , H.C.,Smith , R.F.,Mollinedo , N.S.,McDonald , C.G. Synapse 64(10) 754-64 This study investigated the dendritic morphology of neurons located in the right and left basolateral amygdala (BLA) and infralimbic (IL) cortex following chronic nicotine exposure during adolescence or adulthood. Sprague-Dawley rats were administered subcutaneous injections of nicotine (0.5 mg/kg; free base) or saline three times per week for 2 weeks (six total injections). The dose period began on either postnatal day (P) 32 (adolescent) or P61 (adult). Twenty days following the end of dosing, brains were processed for Golgi-Cox staining, and dendrites from principal neurons in the BLA and pyramidal neurons in the IL were digitally reconstructed in three dimensions. Morphometric analysis revealed a contrasting pattern of BLA dendritic morphology between the adolescent and adult pretreatment groups. In the adult control group, basilar dendritic length did not differ with respect to hemisphere. Nicotine induced robust hemispheric asymmetry by increasing dendritic length in the right hemisphere only. In contrast, adolescent nicotine exposure did not produce significant alteration of basilar dendritic morphology. There was, however, an indication that nicotine eliminated a naturally existing hemispheric asymmetry in the younger cohort. At both ages, nicotine produced a reduction in complexity of the apical tree of principal neurons. Chronic nicotine did not affect the dendritic morphology of pyramidal neurons from the IL in either age group, indicating another dimension of anatomical specificity. Collectively, these data implicate the BLA as a target for lasting neuroplasticity associated with chronic nicotine exposure. Further, hemispheric differences in dendritic morphology were uncovered that depended on the age of nicotine exposure, a finding that underscores the importance of considering laterality when investigating neurodevelopmental effects of drug exposure. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Chronic+nicotine+exposure+produces+lateralized%2C+age-dependent+dendritic+remodeling+in+the+rodent+basolateral+amygdala.
2013 Tobacco Use Among African American Youth Receiving Behavioral Healthcare Services. Breland , A. B.,Nasim , A.,Irons , J. G.,Koch , J.R. The journal of behavioral health services & research 40 88-96 African-American youth with behavioral health problems may be particularly vulnerable to tobacco use and dependence; however, little is known about overall prevalence and factors associated with tobacco use in this population. The present study compared rates of tobacco use for African-Americans (aged 13-17) receiving behavioral healthcare services to state and national prevalence rates. In addition, we examined whether tobacco use prevalence was related to treatment characteristics and services rendered. Retrospective chart reviews were conducted at an urban, public behavioral healthcare agency for youth admitted in 2009. Tobacco use rates among African-Americans receiving behavioral healthcare services were similar to, and in some cases, higher than statewide and national prevalence rates. While tobacco users were more likely to be enrolled in a substance abuse program than in a mental health program, only 2 of 55 youth reporting tobacco use had received documented tobacco cessation treatment. Future work should focus on implementing tobacco cessation prevention and treatment for these youth. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/23307111
2012 Effects of acute stress on acquisition of nicotine conditioned place preference in adolescent rats: a role for corticotropin-releasing factor 1 receptors. Brielmaier , J.,McDonald , C.G.,Smith , R. F. Psychopharmacology 219(1) 73-82 RATIONALE: Studies indicate that adolescence is a time of increased sensitivity to the rewarding effects of nicotine, and that stress is associated with an increased risk for smoking initiation in this age group. It is possible that stress leads to increased nicotine use in adolescence by augmenting its rewarding properties. Corticotropin-releasing factor type 1 receptors (CRF-R1) mediate physiological and behavioral stress responses. They may also mediate stress-induced potentiation of activity in multiple neural substrates implicated in nicotine reward. OBJECTIVES: The aim of the present study was to determine the effect of acute stressor exposure on single trial nicotine conditioned place preference (CPP) in adolescent male rats using a biased CPP procedure and the role of CRF-R1 in this effect. RESULTS: A single episode of intermittent footshock administered 24 h before the start of place conditioning dose-dependently facilitated acquisition of CPP to nicotine (0.2, 0.4, and 0.6 mg/kg). Pretreatment with CP-154,526 (20 mg/kg), a selective CRF-R1 antagonist, 30 min before footshock exposure significantly attenuated the effect of prior stress to facilitate nicotine CPP acquisition. CP-154,526 pretreatment had no effect in animals conditioned with a nicotine dose that produced CPP under non-stress conditions, suggesting a specific role for CRF-R1 following stress. CONCLUSIONS: Taken together, the results suggest that during adolescence, nicotine reward is enhanced by recent stressor exposure in a manner that involves signaling at CRF-R1. Information from studies such as this may be used to inform efforts to prevent and treat adolescent nicotine dependence. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/21720754
2007 Immediate and long-term behavioral effects of a single nicotine injection in adolescent and adult rats. Brielmaier , J.M.,McDonald , C.G.,Smith , R.F. Neurotoxicology and Teratology 29 74-80 We examined the acute rewarding as well as the long-term psychomotor altering effects of nicotine in early adolescent and adult male Sprague-Dawley rats. Place conditioning was used to examine nicotine-induced reward after a single drug pairing. A single pairing of nicotine with the initially non-preferred side of the place conditioning apparatus produced a conditioned place preference (CPP) in early adolescent but not adult animals. One month later, animals were given a nicotine challenge and locomotor activity observed in the open field to characterize age differences in the lasting alterations resulting from this single injection. Adult rats showed tolerance to the locomotor depressant effects of a low dose of nicotine whereas adolescent rats showed tolerance to a higher dose. Regardless of treatment group, animals tested during adolescence responded to the nicotine challenge with less hypoactivity when compared with animals tested as adults. The present results are in agreement with previous studies showing that early adolescent rats are more sensitive to nicotine's rewarding effects and are in accord with studies showing a unique profile of neurobehavioral alterations following nicotine exposure when compared with adults. Such findings are extended here by showing that these differences are seen following only a single pretreatment dose and persist for at least one month after pretreatment. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Immediate+and+long-term+behavioral+effects+of+a+single+nicotine+injection+in+adolescent+and+adult+rats.
2007 Perinatal nicotine exposure eliminates peak in nicotinic acetylcholine receptor response in adolescent rats. Britton , A.F.,Vann , R.E.,Robinson , S.E. . Journal of Pharmacology and Experimental Therapeutics 320(2) 871-876 Maternal smoking is a risk factor associated with nicotine abuse, so the effect of perinatal nicotine exposure was studied on the responsiveness to nicotine across adolescence in the rat. Pregnant Sprague-Dawley rats were implanted with s.c. Alzet osmotic minipumps delivering nicotine (L-nicotine hydrogen tartrate, 2 mg/kg/day free base) or vehicle (0.9% saline) on gestational day 7. There was no effect of nicotine on dam weight gain, food consumption, or water consumption or on the number of live pups or weights at the time of birth. Pups were cross-fostered to obtain the following prenatal/postnatal exposure groups: control/control, nicotine/nicotine, nicotine/control, and control/nicotine. On postnatal days 28, 35, 49, and 63, nicotine-stimulated (86)Rb(+) efflux was measured in synaptosomes prepared from the frontal cortex, hippocampus, striatum (STR), and thalamus (THL), using a previously developed method. Significant effects of treatment and concentration were detected in all four brain regions, and significant effects of age were observed in the STR and THL. Significant interactions of age and treatment were observed in each of the four brain regions. Nicotine-stimulated (86)Rb(+) efflux peaked during adolescence in control rats. However, perinatal exposure to nicotine eliminated this peak during adolescence. These results are consistent with recent behavioral and receptor binding results from other laboratories and are the first direct evidence at the cellular level that the nicotinic acetylcholine receptor response varies during adolescence and is affected by perinatal nicotine exposure. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/17105825
2012 Preclinical evidence that activation of mesolimbic alpha 6 subunit containing nicotinic acetylcholine receptors supports nicotine addiction phenotype. Brunzell , D. H., , Nicotine & Tobacco Research 14(11) 1258-1269 INTRODUCTION: Nicotine is a major psychoactive ingredient in tobacco yet very few individuals quit smoking with the aid of nicotine replacement therapy. Targeted therapies with more selective action at nicotinic acetylcholine receptors (nAChRs) that contain a β2 subunit (β2*nAChRs; *denotes assembly with other subunits) have enjoyed significantly greater success, but exhibit potential for unwanted cardiac, gastrointestinal, and emotive side effects. DISCUSSION: This literature review focuses on the preclinical evidence that suggests that subclasses of β2*nAChRs that assemble with the α6 subunit may provide an effective target for tobacco cessation. α6β2*nAChRs have a highly selective pattern of neuroanatomical expression in catecholaminergic nuclei including the ventral tegmental area and its projection regions. α6β2*nAChRs promote dopamine (DA) neuron activity and DA release in the mesolimbic dopamine system, a brain circuitry that is well-studied for its contributions to addiction behavior. A combination of genetic and pharmacological studies indicates that activation of α6β2*nAChRs is necessary and sufficient for nicotine psychostimulant effects and nicotine self-administration. α6β2*nAChRs support maintenance of nicotine use, support the conditioned reinforcing effects of drug-associated cues, and regulate nicotine withdrawal. CONCLUSIONS: These data suggest that α6β2*nAChRs represent a critical pool of high affinity β2*nAChRs that regulates nicotine dependence phenotype and suggest that inhibition of these receptors may provide an effective strategy for tobacco cessation therapy. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Preclinical+evidence+that+activation+of+mesolimbic+alpha+6+subunit+containing+nicotinic+acetylcholine+receptors+supports+nicotine+addiction+phenotype.
2011 Alpha7 nicotinic acetylcholine receptors modulate motivation to self-administer nicotine: implications for smoking and schizophrenia. Brunzell , D. H.,McIntosh , J.M. Neuropsychopharmacology 37(5) 1134-1143 Individuals diagnosed with schizophrenia have an exceptionally high risk for tobacco dependence. Postmortem studies show that these individuals have significant reductions in α7 nicotinic acetylcholine receptors (nAChRs) in several brain areas. Decreased α7-mediated function might not only be linked to schizophrenia but also to increased tobacco consumption. The purpose of this study was to determine whether pharmacological blockade of α7 nAChRs would increase motivation of rats to intravenously self-administer nicotine (NIC) during a progressive ratio schedule of reinforcement (PR). Before PR, rats received local infusions of 0, 10, or 20 pmol of a selective α7 nAChR antagonist, α-conotoxin ArIB [V11L,V16D] (ArIB) into the nucleus accumbens (NAc) shell or the anterior cingulate cortex, brain areas that contribute to motivation for drug reward. We additionally sought to determine whether local infusion of 0, 10, or 40 nmol of a selective α7 nAChR agonist, PNU 282987, into these brain areas would decrease motivation for NIC use. Infusion of ArIB into the NAc shell and anterior cingulate cortex resulted in a significant increase in active lever pressing, breakpoints, and NIC intake, suggesting that a decrease in α7 nAChR function increases motivation to work for NIC. In contrast, PNU 282987 infusion resulted in reductions in these measures when administered into the NAc shell, but had no effect after administration into the anterior cingulate cortex. These data identify reduction of α7 nAChR function as a potential mechanism for elevated tobacco use in schizophrenia and also identify activation of α7 nAChRs as a potential strategy for tobacco cessation therapy. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/22169946
2014 Diverse strategies targeting α7 homomeric and α6β2* heteromeric nicotinic acetylcholine receptors for smoking cessation. Brunzell , D.H.,McIntosh , J.M.,Papke , R.L. Annals of the New York Academy of Science 1327 27-45 Preclinical studies suggest that a diversity of nicotinic acetylcholine receptors (nAChRs) with different sensitivities to nicotine may contribute to tobacco addiction. Using rodent intravenous nicotine self-administration as a preclinical model with good predictive validity for therapeutic efficacy for tobacco cessation, investigators have identified heteromeric α6β2* and homomeric α7 nAChRs as promising novel therapeutic targets to promote smoking abstinence (*denotes possible assembly with other subunits). The data suggest that diverse strategies that target these subclasses of nAChRs, namely inhibition of α6β2* nAChRs and stimulation of α7 nAChRs, will support tobacco cessation. α6β2* nAChRs, members of the high-affinity family of β2* nAChRs, function similarly to α4β2* nAChRs, the primary target of the FDA-approved drug varenicline, but have a much more selective neuroanatomical pattern of expression in catecholaminergic nuclei. Although activation of β2* nAChRs facilitates nicotine self-administration, stimulation of α7 nAChRs appears to negatively modulate both nicotine reinforcement and β2* nAChR function in the mesolimbic dopamine system. Although challenges and caveats must be considered in the development of therapeutics that target these nAChR subpopulations, an accumulation of data suggests that α7 nAChR agonists, partial agonists, or positive allosteric modulators and α6β2* nAChR antagonists, partial agonists, or negative allosteric modulators may prove to be effective therapeutics for tobacco cessation. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/24730978
2015 Nicotinic receptor contributions to smoking: Insights from human studies and animal models. Brunzell , D.H.,Stafford , A.M.,Dixon , C.I. Current Addiction Reports 2(1) 33-46 It is becoming increasingly evident that a variety of factors contribute to smoking behavior. Nicotine is a constituent of tobacco smoke that exerts its psychoactive effects via binding to nicotinic acetylcholine receptors (nAChRs) in brain. Human genetic studies have identified polymorphisms in nAChR genes, which predict vulnerability to risk for tobacco dependence. In vitro studies and animal models have identified the functional relevance of specific polymorphisms. Together with animal behavioral models, which parse behaviors believed to contribute to tobacco use in humans, these studies demonstrate that nicotine action at a diversity of nAChRs is important for expression of independent behavioral phenotypes, which support smoking behavior. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/26301171
2014 The N2 ERP component as an index of impaired cognitive control in smokers. Buzzell , G. A.,Fedota , J.R.,Roberts , D. M.,McDonald , C.G. Neuroscience Letters 563 61-65 Impaired cognitive control has been proposed as a hallmark of nicotine dependence and is thought to arise, in part, from synaptic alterations in anterior cingulate cortex (ACC), a primary component of the dopamine reward pathway. The N2 component of the event-related potential (ERP) appears to index a cognitive control process in paradigms such as the visual go/no-go task. Moreover, as dipole-modeling has suggested that the neural generator of the N2 component can be localized to the ACC, this component may prove useful for investigating impairments of cognitive control in smokers. Given conflicting reports of whether the N2 is reduced in smokers (as compared to non-smoker controls), the current study further examined the suitability of this component as an index for impaired cognitive control in smokers. Smokers and non-smokers performed a visual go/no-go task while electroencephalogram (EEG) was recorded. As predicted, the no-go N2 of smokers was significantly smaller than that of non-smoker controls, while the no-go P3 did not differ between groups. Importantly, behavioral performance (reaction time and accuracy) did not differ between smokers and nonsmokers, which might reflect the low levels of nicotine dependence (assessed by the Fagerstrom test) in our sample. The observed N2 modulation in the absence of behavioral impairments provides evidence for the utility of the N2 component as a sensitive measure of impaired cognitive control in smokers, even in those with low levels of nicotine dependence. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/24486891
2004 The effects of smoking on blood platelet monoamine oxidase-b activity in southwestern Virginia female teenage smokers. Castagnoli , K.,Wu , X.,Crawford , H.J. In P. Meszaros F. Piercy A. Huebner H. Crawford K. Castagnoli. (Eds.). Adolescent Females & Smoking. Monograph published by the Center for Information Technology Impacts on Children Youth and Families. Blacksburg VA: Virginia Tech.
2011 ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure. Chen , J.,Brunzell , D.H.,Jackson , K.,vander Vaart , A.,Ma , J.Z.,Payne , T.J.,Chen , X. PloS One 6(12) e28790 Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/22205969
2007 RhoA, encoding a Rho GTPase, is associated with smoking initiation. Chen , X.,Che , Y.,Zhang , L.,Putman , A.H.,Damaj , I.,Martin , B.R.,Kendler , K.S.,Miles , M.F. Genes Brain Behav 6(8) 689-97 We used microarray analysis of acute nicotine responses in mouse brain to choose rationale candidates for human association studies on tobacco smoking and nicotine dependence (ND). Microarray studies on the time-course of acute response to nicotine in mouse brain identified 95 genes regulated in ventral tegmental area. Among these, 30 genes were part of a gene network, with functions relevant to neural plasticity. On this basis and their known roles in drug abuse or synaptic plasticity, we chose the genes RhoA and Ywhag as candidates for human association studies. A synteny search identified human orthologs and we investigated their role in tobacco smoking and ND in a human case-control association study. We genotyped five and three single nucleotide polymorphisms from the RhoA and Ywhag genes, respectively. Both single marker and haplotype analyses were negative for the Ywhag gene. For the RhoA gene, rs2878298 showed highly significant genotypic association with both smoking initiation (SI) and ND (P = 0.00005 for SI and P = 0.0007 for ND). In the allelic analyses, rs2878298 was only significant for SI. In the multimarker haplotype analyses, significant association with SI was found for the RhoA gene (empirical global P values ranged from 9 x 10(-5) to 10(-5)). In all multimarker combinations analyzed, with or without inclusion of the single most significant marker rs2878298, identical risk and protective haplotypes were identified. Our results indicated that the RhoA gene is likely involved in initiation of tobacco smoking and ND. Replication and future model system studies will be needed to validate the role of RhoA gene in SI and ND. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/17284169
2009, October 5 Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence. Chen , X.,Chen , J.,Williamson , V.S.,An , S.S.,Hettema , J.M.,Aggen , S.H.,Neale , M.C.,Kendler , K.S. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 150B(7) 926-933 Nicotinic acetylcholine receptors bind to nicotine and initiate the physiological and pharmacological responses to tobacco smoking. In this report, we studied the association of α5 and α3 subunits with nicotine dependence and with the symptoms of alcohol and cannabis abuse and dependence in two independent epidemiological samples (n = 815 and 1,121, respectively). In this study, seven single nucleotide polymorphisms were genotyped in the CHRNA5 and CHRNA3 genes. In both samples, we found that the same alleles of rs16969968 (P = 0.0068 and 0.0028) and rs1051730 (P = 0.0237 and 0.0039) were significantly associated with the scores of Fagerström test for nicotine dependence (FTND). In the analyses of the symptoms of abuse/dependence of alcohol and cannabis, we found that rs16969968 and rs1051730 were significantly associated with the symptoms of alcohol abuse or dependence (P = 0.0072 and 0.0057) in the combined sample, but the associated alleles were the opposite of that of FTND. No association with cannabis abuse/dependence was found. These results suggested that the α5 and α3 subunits play a significant role in both nicotine dependence and alcohol abuse/dependence. However, the opposite effects with nicotine dependence and alcohol abuse/dependence were puzzling and future studies are necessary to resolve this issue. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/19132693
2013 US Children's Acquisition of Tobacco Media Literacy Skills: A Focus Group Analysis. Chen , Y. C.,Kaestle , C.E.,Estabrooks , P.,Zoellner , J. Journal of Children and Media (ahead-of-print) 1-19 Pro-tobacco messages in media play an important role in initiating smoking behavior among children, but can be addressed in health promotion media literacy interventions. Children from Southwest Virginia, US (age range: 8-14, N = 19) who participated in a tobacco media literacy intervention were invited to discuss their learning and understanding of tobacco media literacy in three focus groups. Data were analyzed using thematic analysis and sensitizing concepts based on a comprehensive theoretical framework. Responses to the intervention were largely categorized into awareness of absent health messages, perceived media influences, and critical evaluation. Unanticipated themes also emerged, such as enthusiasm for media production, desirability of commercials despite the intervention, and an excitement to share with family. These findings not only have implications for the development of health promotion media literacy, but also add additional dimensions to advance theoretical development. Virginia Tech https://www.tandfonline.com/doi/abs/10.1080/17482798.2012.755633
2008 Cannabinoid receptor 1 gene association with nicotine dependence. Chen , X.,Williamson , V.S.,An , S.S.,Hettema , J.M.,Aggen , S.H.,Neale , M.C.,Kendler , K.S. Archives of General Psychiatry 65(7) 816-823 CONTEXT: The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence. OBJECTIVE: To test the hypothesis that the CNR1 gene is associated with nicotine dependence. DESIGN: Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n = 688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerström Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry. PARTICIPANTS: White patients aged 18 to 65 years who met the criteria of inclusion. MAIN OUTCOME MEASURES: Fagerström Tolerance Questionnaire and FTND scores. RESULTS: Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P < .001 and P = .009, respectively). CONCLUSION: Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/18606954
2012 The mediating and moderating effects of parent and peer influences upon drug use among African American adolescents. Clark , T.T.,Belgrave , F.Z.,Abell , M. Journal of Black Psychology 38(1) 52-80 This study recruited 567 African American youth (mean age = 15.27 years; 65.1% girls) to examine the role of parent and peer contexts on drug use among African American adolescents. Data were collected on demographics, drug refusal efficacy, drug use, and various psychosocial factors including family and peer factors. When controlling for age and gender, parental monitoring and peer risky behavior completely mediated the relationship between parental attitudes toward drug use and drug refusal efficacy and partially mediated the relationship between parental attitudes toward drug use and current alcohol use. Only peer risky behavior mediated the relationships between parental attitudes toward drug use and current tobacco and marijuana use. Results also revealed several salient moderating relationships. Implications for prevention programs are provided and include strengthening current parenting skills and focusing efforts on fostering the mother-adolescent relationship.
2012 Family factors and mediators of substance use among African American adolescents. Clark , T.T.,Nguyen , A.B. Journal of Drug Issues 42(4) 358-372 This study uses a sample of 424 African American 8th- and 12th-grade students (mean age = 16.55; 65.1% girls) in the United States to examine how family protective factors explain cultural and school protective factors that prevent substance use. Questionnaires were administered between 2007 and 2009. Using structural equation modeling, results indicated that cultural and school factors partially mediated the relationship between family factors and lifetime substance use. School factors fully mediated the relationship between cultural factors and lifetime substance use. The findings suggest that parents promote cultural attributes, which in turn promotes school achievement, and in turn contributes to lower substance use. Limitations of the study, and implications for future research and prevention programs are discussed.
2004 Why are some teenage girls more vulnerable to start smoking? Crawford , H.J.,Loe , J.,Wan , L. A preliminary grant report on cognitive EEG and behavioral correlates. In P. Meszaros F. Piercy A. Huebner H. Crawford K. Castagnoli. (Eds.). Adolescent Females & Smoking. Monograph published by the Center for Information Technology Impacts on Children Youth and Families. Blacksburg VA: Virginia Tech. Virginia Tech
2004 Female adolescent smoking: a Delphi study on best prevention practices. Davis , S.,Piercy , F.,Meszaros , P.S.,Huebner , A.,Shettler , L.,Matheson , J. Journal of Drug Education 34(3) 295-311 The present researchers used a multi-wave Delphi methodology to determine what 14 knowledgeable substance abuse professionals believe are the most appropriate smoking prevention practices for female adolescents. While there was some agreement with the emerging literature, particularly on weight control issues and parental involvement, there was also endorsement of items that appear to be equally salient for both males and females. While the panelists generally acknowledged differential risk factors for females, and the need for prevention programming around these risk factors, more research on gender specific programming is needed before prevention experts are ready to agree on clear and specific practices for adolescent females. Virginia Tech https://www.ncbi.nlm.nih.gov/pubmed/15648889
2017 Nicotine-induced and D1-receptor-dependent dendritic remodeling in a subset of dorsolateral striatum medium spiny neurons. Ehlinger , D.G.,Burke , J.C.,McDonald , C.G.,Smith , R.F.,Bergstrom , H.C. Neuroscience 356 242-254 Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. Whether MSN dendrites in the dorsal striatum undergo a similar pattern of nicotine-induced structural remodeling is unknown. A morphometric analysis of Golgi-stained MSNs in rat revealed a natural asymmetry in dendritic morphology across the mediolateral axis, with larger, more complex MSNs found in the dorsolateral striatum (DLS). Chronic nicotine produced a lasting (at least 21day) expansion in the dendritic complexity of MSNs in the DLS, but not dorsomedial striatum (DMS). Given prior evidence that MSN subtypes can be distinguished based on dendritic morphology, MSNs were segregated into morphological subpopulations based on the number of primary dendrites. Analysis of these subpopulations revealed that DLS MSNs with more primary dendrites were selectively remodeled by chronic nicotine exposure and remodeling was specific to the distal-most portions of the dendritic arbor. Co-administration of the dopamine D1 receptor (D1R) antagonist SCH23390 completely reversed the selective effects of nicotine on DLS MSN dendrite morphology, supporting a causal role for dopamine signaling at D1 receptors in nicotine-induced dendrite restructuring. Considering the functional importance of the DLS in shaping and expressing habitual behavior, these data support a model in which nicotine induces persistent and selective changes in the circuit connectivity of the DLS that may promote and sustain addiction-related behavior. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Nicotine-induced+and+D1-receptor-dependent+dendritic+remodeling+in+a+subset+of+dorsolateral+striatum+medium+spiny+neurons.
2006 Long-term behavioral and developmental consequences of pre- and perinatal nicotine. Eppolito , A.K.,Smith , R.F. Pharamcology Biochemistry and Behavior 85 835-841 Research has shown that cigarette use during pregnancy can result in increased fetal mortality, sudden infant death syndrome, and behavioral and attentional disorders during childhood. Neurochemical and behavioral consequences of prenatal nicotine exposure have been well documented although few studies have examined long-term behavioral consequences that persist into adulthood. In this study, fifty-eight male and female Long-Evans rats were exposed to chronic nicotine prenatally and postnatally via subcutaneous infusions (0.96 mg/kg/day) in the dam. Nicotine exposure continued in the pups via maternal milk until the dams' osmotic mini-pumps became exhausted at approximately postnatal day (P) 11. At weaning, animals were group housed until behavioral testing at P60 to assess spatial learning and memory in the Morris water maze (MWM). Mild deficits in spatial learning were observed in nicotine-exposed females. These behavioral differences were accompanied by significant reduction in weight gain of nicotine-exposed females beginning at puberty, suggesting a hormonal interaction. Long-term effects of nicotine exposure were less striking in males. Nicotine-exposed males had significantly slower swim speeds than controls, but latency to reach the hidden platform was equal between groups by the conclusion of testing. Weight gain in males did not differ between groups as a result of prenatal nicotine exposure. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/17196635
2010, January 7 Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior. Eppolito , A.K.,Bachus , S.E.,McDonald , C.G.,Meador-Woodruff , J.H.,Smith , R.F. Neurotoxicol Teratol 32(3) 336-45 Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96 mg/kg/day or 2.0 mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the α4, α7, and β2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/20060465
2005 Community participation in the treatment development process using community development teams. Evans , S.W.,Green , A.L.,Serpell , Z.N. Journal of Clinical Child and Adolescent Psychology 34(4) 765-771 Little literature exists about methods for adapting research-based treatments to typical practice settings. This report describes a 2-step process and associated methods used to adapt a school-based treatment program for middle-school youth with attention deficit hyperactivity disorder (ADHD) that operates in a controlled setting to one that can operate in a typical practice setting. Step 1 included a feasibility study that yielded important findings regarding potential obstacles to successful implementation. These data, along with original treatment manuals and literature on treatments for youth with ADHD, were utilized for Step 2--the Community Development Team (CDT) process. Data collected about the CDT process indicate that its strengths outweigh potential limitations. These methods are discussed in the context of successful collaborative procedures for developing and evaluating research-based treatments in practice settings. https://www.ncbi.nlm.nih.gov/pubmed/16232073
2007 Cumulative benefits of secondary school-based treatment of students with attention deficit hyperactivity disorder. Evans , S.W.,Serpell , Z.N.,Schultz , B.K.,Pastor , D.A. School Psychology Review 36(2) 256-273 School-based services are well suited for youth with chronic conditions who manifest much of their impairment in the school setting, such as youth with attention deficit hyperactivity disorder (ADHD). A significant literature on such programs at the elementary level exists, but little has been developed and tested at the secondary level. The current study is a 3-year treatment outcome study of a school-based training and consultation program for middle school youth with ADHD. Social and academic outcomes for program recipients were compared to that of participants in a community care control group. Findings revealed cumulative long-term benefits for the treatment group as measured by parent ratings of ADHD symptoms and social functioning. Although teacher and parent reports indicated no cumulative academic benefits, within-year analyses suggested a trend toward benefits in student grade point average. Implications for the treatment of ADHD in secondary schools are discussed.
2006 Developing coordinated, multimodal, school-based treatment for young adolescents with ADHD. Evans , S.W.,Timmins , B.,Sibley , M.,White , L.C.,Serpell , Z.N.,Schultz , B. Education and Treatment of Children 29(2) 359-378 Adolescents with ADHD experience serious impairment that taxes our education, mental health, and healthcare systems as well as the children and families. The development and evaluation of effective treatments for these youth have lagged far behind that of many other disorders and age groups. This manuscript describes the treatment development process for a school-based comprehensive care model for treating middle-school aged youth with ADHD. An overview of the development process is described as well as future directions. Specific interventions that comprise the Challenging Horizons Program (CHP) are explained as well as their feasibility in public middle schools.
2014 Developmental alterations in locomotor and anxiety-like behavior as a function of D1 and D2 mRNA expression. Falco , A. M.,McDonald , C.G.,Bachus , S. E.,Smith , R.F. Behavioural Brain Research 260 25-33 The majority of smokers start smoking in adolescence, beginning a potentially lifelong struggle with nicotine use and abuse. In rodent models of the effects of nicotine, the drug has been shown to elicit both locomotor and anxiety-like behavioral effects. Research suggests that these behavioral effects may be due in part to dopamine (DA) receptors D1 and D2 in the mesolimbic system, specifically the nucleus accumbens (NAc). We examined early adolescent (P28), late adolescent (P45), and adult (P80) male Long-Evans rats in the elevated plus maze (EPM) under normal conditions and the open field (OF) post-nicotine in order to test locomotor and anxiety-like behavior. These behavioral findings were then correlated with expression of DA D1 and D2 mRNA levels as determined via in situ hybridization. Nicotine-induced locomotor behavior was found to be significantly different between age groups. After a single injection of nicotine, early adolescents exhibited increases in locomotor behavior, whereas both late adolescents and adults responded with decreases in locomotor behavior. In addition, it was found that among, early adolescents, open arm and center time in the EPM were negatively correlated with D2 mRNA expression. In contrast, among adults, distance traveled in the center and center time in the OF were negatively correlated with D2 mRNA expression. This study suggests that DA D2 receptors play a role in anxiety-like behavior and that the relationship between observed anxiety-like behaviors and D2 receptor expression changes through the lifespan. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/24239691
2014 Anxiety status affects nicotine- and baclofen-induced locomotor activity, anxiety, and single trial conditioned place preference in male adolescent rats. Falco , A.M.,McDonald , C.G.,Smith , R.F. Developmental Psychobiology 56(6) 1352-1364 Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety-like behavior on single-trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety-like behavior in rats divided into high-anxiety and low-anxiety groups. Baclofen decreased locomotor behavior in high-anxiety rats. Baclofen alone failed to produce differences in anxiety-like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High- and low-anxiety groups also showed differences in single-trial nicotine-induced place preference. Only high-anxiety rats formed place preference to nicotine, while rats in the low-anxiety group formed no conditioned place preference. These results suggest that among adolescents, high-anxiety individuals are more likely to show preference for nicotine than low-anxiety individuals. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/24719177
2013 Stress among African American emerging adults: The role of family and cultural factors. Hood , K.,Brevard , J.,Nguyen , A.B.,Belgrave , F. Journal of Child and Family Studies 22(1) 76-84 The aim of this study was to examine the effects of family and cultural variables on stress among African American emerging adults. Data from this study was collected as part of a larger study that examined cultural, family, and contextual factors and smoking among African American youth in 5th, 8th, and 12th grades. Data were collected from high school seniors at the end of their 12th grade year and 6 months post high school. Multiple regression analyses were conducted to determine whether racial identity, family cohesion, and parental monitoring influence students' perceived frequency of stress. Higher levels of racial identity were associated with more perceived stress. There were no significant main effects for either parental monitoring or family cohesion on stress. There were significant interactions between racial identity and parental monitoring and between parental monitoring and family cohesion. Study implications are discussed regarding the importance of stress reduction programs for African American emerging adults and for parents of these adults. Virginia Commonwealth University
2004 Factors associated with rural female adolescent smoking: a systematic review. Huebner , A.,Shettler , L.,Matheson , J.L.,Meszaros , P.,Piercy , F.,Davis , S. In P. Meszaros F. Piercy A. Huebner H. Crawford K. Castagnoli. (Eds.). Adolescent Females & Smoking. Monograph published by the Center for Information Technology Impacts on Children Youth and Families. Blacksburg VA: Virginia Tech.
2006 Examining ethnic differences in predictors of female adolescent smoking in rural Virginia. Huebner , A.J.,Shettler , L.,Matheson , J.L.,Meszaros , P.S.,Piercy , F.P.,Davis , S.D. Journal of Child & Adolescent Substance Abuse 15(3) 63-81 We examined the salience of multiple ecological factors (individual, family, peer, school, and community) as differential predictors of smoking for adolescent African-Americans and Whites in a sample of 2,029 7th-12th grade girls from a Mid-Atlantic southeastern state. Hierarchical regression analyses revealed that significant predictors of smoking in the White female model included coping by taking drugs, grades, frequency of using alcohol, frequency of using marijuana, parent quality, and perceived availability of cigarettes. Significant predictors of smoking in the African-American female model included coping by taking drugs, attempted suicide, frequency of alcohol use, frequency of marijuana use, hours spent in club activities, hours spent in sports, and socioeconomic status. Implications for prevention and intervention programs are discussed.
2005 Factors associated with former smokes among female adolescents in rural Virginia. Huebner , A.J.,Shettler , L.,Matheson , J.L.,Meszaros , P.S.,Piercy , F.P.,Davis , S.D. Addictive Behaviors 30 167-173
2015 An animal model of fetal alcohol spectrum disorder: Trace conditioning as a window to inform memory deficits and intervention tactics. Hunt , P.S.,Barnet , R.C. Physiology & Behavior 148(1) 36-44 Animal models of Fetal Alcohol Spectrum Disorders (FASD) afford the unique capacity to precisely control timing of alcohol exposure and alcohol exposure amounts in the developing animal. These models have powerfully informed neurophysiological alterations associated with fetal and perinatal alcohol. In two experiments presented here we expand use of the Pavlovian Trace Conditioning procedure to examine cognitive deficits and intervention strategies in a rat model of FASD. Rat pups were exposed to 5 g/kg/day ethanol on postnatal days (PD) 4-9, simulating alcohol exposure in the third trimester in humans. During early adolescence, approximately PD 30, the rats were trained in the trace conditioning task in which a light conditioned stimulus (CS) and shock unconditioned stimulus (US) were paired but separated by a 10-s stimulus free trace interval. Learning was assessed in freezing behavior during shock-free tests. Experiment 1 revealed that neonatal ethanol exposure significantly impaired hippocampus-dependent trace conditioning relative to controls. In Experiment 2 a serial compound conditioning procedure known as 'gap filling' completely reversed the ethanol-induced deficit in trace conditioning. We also discuss prior data regarding the beneficial effects of supplemental choline and novel preliminary data regarding the pharmacological cognitive enhancer physostigmine, both of which mitigate the alcohol-induced cognitive deficit otherwise seen in trace conditioning controls. We suggest trace conditioning as a useful tool for characterizing some of the core cognitive deficits seen in FASD, and as a model for developing effective environmental as well as nutritional and pharmacological interventions. https://www.ncbi.nlm.nih.gov/pubmed/25477227
2009, July 18 Characterization of pharmacological and behavioral differences to nicotine in C57B1/6 and DBA/2 mice. Jackson , K.J.,Walters , C.L.,Miles , M.F.,Martin , B.R.,Damaj , M.I. Neuropharmacology. 57(4) 347-55 Approximately 50-70% of the risk for developing nicotine dependence is attributed to genetics; therefore, it is of great significance to characterize the genetic mechanisms involved in nicotine reinforcement and dependence in hopes of generating better smoking cessation therapies. The overall goal of these studies was to characterize behavioral and pharmacological responses to nicotine in C57Bl/6 (B6) and DBA/2 (D2) mice, two inbred strains commonly used for genetic studies on behavioral traits. B6 and D2 mice where subjected to a battery of behavioral tests to measure nicotine's acute effects, calcium-mediated antinociceptive responses, tolerance to chronic treatment with osmotic mini pumps, and following three days of nicotine withdrawal. In general, D2 mice were less sensitive than B6 mice to the acute effects of nicotine, but were more sensitive to blockade of nicotine-induced antinociceptive responses by a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. B6, but not D2 mice, developed tolerance to nicotine and nicotine conditioned place preference (CPP). While B6 and D2 mice both expressed some physical withdrawal signs, affective withdrawal signs were not evident in D2 mice. These results provide a thorough, simultaneous evaluation of the pharmacological and behavioral differences to experimenter-administered nicotine as measured in several behavioral tests of aspects that contribute to smoking behavior. The B6 and D2 strains show wide phenotypic differences in their responses to acute or chronic nicotine. These results suggest that these strains may be useful progenitors for future genetic studies on nicotine behaviors across batteries of mouse lines such as the BXD recombinant inbred panel. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/19619563
2013 Not so cool? Menthol's discovered actions on the nicotinic receptor and its implications for nicotine addiction. Kabbani , N., , Frontiers in Pharmacology 4(95) Nicotine cigarette smoke is a large public health burden worldwide, contributing to various types of disease. Anti-tobacco media campaigns and control programs have significantly reduced smoking in the United States, yet trends for menthol cigarette smoking have not been as promising. Menthol cigarette smoking is particularly prevalent among young adults and African Americans, with implications for long-term impacts on health care. Continuing high rates of menthol cigarette addiction call into question the role of menthol in nicotine addiction. To date, a biological basis for the high rate of addiction and relapse among menthol cigarette smokers has not been defined. Studies have demonstrated a role for menthol in the metabolism of nicotine in the body. More recent findings now reveal an interaction between menthol and the nicotinic acetylcholine (nACh) receptor in cells. This receptor is central to the actions of nicotine in the brain, and plays an important role in nicotine addiction. The newly discovered effect of menthol on nACh receptors may begin to explain the unique addictive properties of menthol cigarettes. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Not+so+cool%3F+Menthol%27s+discovered+actions+on+the+nicotinic+receptor+and+its+implications+for+nicotine+addiction.
2013 Pilot evaluation of a media literacy program for tobacco prevention targeting early adolescents shows mixed results. Kaestle , C. E.,Chen , Y.,Estabrooks , P. A.,Zoellner , J.,Bigby , B. American Journal of Health Promotion. 6 366-9 PURPOSE: The purpose of this pilot study was to assess the impact of media literacy for tobacco prevention for youth delivered through a community site. DESIGN: A randomized pretest-posttest evaluation design with matched-contact treatment and control conditions. SETTING: The pilot study was delivered through the YMCA in a lower-income suburban and rural area of Southwest Virginia, a region long tied, both economically and culturally, to the tobacco industry. SUBJECTS: Children ages 8 to 14 (76% white, 58% female) participated in the study (n = 38). INTERVENTION: The intervention was an antismoking media literacy program (five 1-hour lessons) compared with a matched-contact creative writing control program. MEASURES: General media literacy, three domains of tobacco-specific media literacy ("authors and audiences," "messages and meanings," and "representation and reality"), tobacco attitudes, and future expectations were assessed. ANALYSIS: Multiple regression modeling assessed the impact of the intervention, controlling for pretest measures, age, and sex. RESULTS: General media literacy and tobacco-specific "authors and audiences" media literacy improved significantly for treatment compared with control (p < .05); results for other tobacco-specific media literacy measures and for tobacco attitudes were not significant. Future expectations of smoking increased significantly for treatment participants ages 10 and younger (p < .05). CONCLUSION: Mixed results indicated that improvements in media literacy are accompanied by an increase in future expectations to smoke for younger children. Virginia Tech https://www.ncbi.nlm.nih.gov/pubmed/23458374
2009 How girls and boys get tobacco: adults and other sources. Kaestle , C.E., , Journal of Adolescent Health 45(2) 208-10 This study of current tobacco users from the 2005 Virginia Youth Tobacco Survey (N = 426) finds that girls were significantly more likely to receive cigarettes for free, particularly from adults, and were also more likely to receive cigars or cigarillos for free, but were more likely to buy smokeless tobacco from a store compared to boys. Virginia Tech https://www.ncbi.nlm.nih.gov/pubmed/19628150
2015 Age of smoking milestones: Longitudinal inconsistencies and recanting. Kaestle , C.E., , Journal of Adolescent Health 56(4) 382-388 PURPOSE: To determine (1) how reports of the ages of first cigarette smoked and daily smoking onset change from adolescence through emerging adulthood and into young adulthood and (2) what predicts reporting inconsistencies and recanting for both smoking milestones. METHODS: Multinomial logistic regression models compared relative risks of the following: (1) consistent reporting of milestone age (reference group); (2) recanting at either subsequent wave; or (3) inconsistent reporting of age in at least one subsequent wave, using data from Waves I, III, and IV of the National Longitudinal Study of Adolescent to Adult Health. RESULTS: Instability and forward telescoping between adolescence and emerging adulthood leveled off by young adulthood. For smoking first cigarette, those who started younger had more inconsistencies and recanting than those who started later, as did African-American, Latino, and Asian respondents compared with non-Latino white respondents. Native American respondents also had higher relative risks of recanting, as did those with low parental education. Males were more inconsistent than females. Depression, same-sex attractions or relationships, and family structure were not associated with reporting stability. Binge drinking, marijuana, and other illegal drugs were associated with lower levels of recanting. For age of daily smoking, starting older versus younger, sex, race, ethnicity, and use of marijuana were significant predictors of report stability. CONCLUSIONS: Stage of life may influence forward telescoping in smoking self-reports. Stability of reports of adolescent smoking by emerging and young adults in the United States appears biased by age of onset, sex, race, and other substance use. Virginia Tech https://www.ncbi.nlm.nih.gov/pubmed/25659993
2010 Targeting High-Risk Neighborhoods for Tobacco Prevention Education in Schools. Kaestle , E. C.,Wiles , B.B. American Journal of Public Health 100(9) 1708-13 OBJECTIVES: We examined whether individual and neighborhood characteristics associated with smoking were also predictive of exposure to smoking prevention education in schools, to determine whether education programs were targeted appropriately to reach neighborhoods with the greatest need. METHODS: We merged data from 2 sources-the 2005 Virginia Youth Tobacco Survey (n = 2208) and the Census 2000 School District Demographics Project-and used binary multilevel models with random effects to determine whether the same demographic characteristics and neighborhood characteristics predicted both adolescent smoking and exposure to prevention programs. RESULTS: We found that although light, medium, and heavy smoking rates were higher in neighborhoods of lower socioeconomic status (relative risk ratio = 1.49, 1.36, and 1.65, respectively), prevention programs were less available in those areas (odds ratio = 0.82). CONCLUSIONS: Our study indicates that school prevention programs are not being effectively targeted and that more effective ways to reach high-risk and disadvantaged neighborhoods are needed. Virginia Tech https://www.ncbi.nlm.nih.gov/pubmed/20019323
2013 Early Smoking Onset and Risk for Subsequent Nicotine Dependence: A Monozygotic Co-Twin Control Study. Kendler , K. S.,Myers , J.,Damaj , M. I.,Chen , X. American Journal of Psychiatry 170(4) 408-413 OBJECTIVE: Early onset of regular smoking is associated with an elevated risk for later nicotine dependence. Whether or not this association is causal is unknown and has substantial public policy implications. METHOD: The authors used a monozygotic co-twin control study design. Pairs were selected from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders for discordance in age at onset of regular smoking. Nicotine dependence was measured by the Fagerström test for nicotine dependence and level of craving. RESULTS: The authors identified 175 male-male and 69 female-female monozygotic twin pairs who differed by at least 2 years in age at onset of regular smoking. During their period of heaviest smoking, the twin who began smoking earlier had significantly higher Fagerström test scores in both the male-male (Cohen's d=0.20) and female-female twin pairs (d=0.26). Craving for cigarettes when unable to smoke was also higher in the early-onset member in both groups (male pairs, d=0.38; female pairs, d=0.25). The early-onset smoking twin did not differ from the later-onset twin in symptoms of alcohol or cannabis abuse or dependence, current alcohol use, or maximal level of cannabis, sedative, stimulant, or cocaine use. CONCLUSIONS: Controlling for genetic and familial-environmental effects, age at onset of regular smoking predicted level of nicotine dependence. Consistent with the animal literature, these findings suggest that in humans, early nicotine exposure directly increases level of later nicotine dependence. These results should be interpreted in the context of the methodological strengths and limitations of the monozygotic co-twin design. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/23318372
2007 Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Kendler , K.S.,Myers , J.M.,Prescott , C.A. Arch Gen Psychiatry 64(11) 1313-1320 CONTEXT: Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. OBJECTIVE: To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. DESIGN: Lifetime history by structured clinical interview. SETTING: General community. PARTICIPANTS: Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. RESULTS: Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. CONCLUSIONS: The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence appear to be specific to those substances. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Specificity+of+genetic+and+environmental+risk+factors+for+symptoms+of+cannabis%2C+cocaine%2C+alcohol%2C+caffeine%2C+and+nicotine+dependence.
2016 Alpha 7 nicotinic receptor coupling to heterotrimeric G proteins modulates RhoA activation, cytoskeletal motility, and structural growth. King , J. R.,Kabbani , N. Journal of Neurochemistry 138(4) 532-45 Nicotinic acetylcholine receptors (nAChRs) modulate the growth and structure of neurons throughout the nervous system. Ligand stimulation of the α7 nAChR has been shown to regulate the large heterotrimeric GTP-binding protein (G protein) signaling in various types of cells. Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth. Specifically, choline treatment was found to attenuate the velocity of microtubule growth at the growth cone and decrease the rate of actin polymerization throughout the cell. The effects of α7 nAChR activation were abolished by expression of a dominant negative α7 nAChR (α7345-348A ) deficient in G protein coupling. Proteomic analysis of immunoprecipitated α7 nAChR complexes from differentiating PC12 cells and synaptic fractions of the developing mouse hippocampus revealed the existence of Rho GTPase-regulating guanine nucleotide exchange factors within α7 nAChR interactomes. These findings underscore the role of α7 nAChR/G protein in cytoskeletal regulation during neurite growth. This image depicts the hypothesized interaction of the traditionally ionotropic α7 nicotinic acetylcholine receptor (α7 nAChR) and its ability to interact and signal through both large and small G proteins, leading to the regulation of cytoskeletal growth. Using differentiated PC12 cells, and the specific agonist choline, it was shown that α7 nAChR/G protein interactions mediate both short- and long-term neurite growth dynamics through increased RhoA activation. Activation of RhoA was shown to decrease actin polymerization, and lead to an overall decrease in neurite growth via regulation of the microtubule network. Cover Image for this issue: doi: 10.1111/jnc.13330. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Alpha+7+nicotinic+receptor+coupling+to+heterotrimeric+G+proteins+modulates+RhoA+activation%2C+cytoskeletal+motility%2C+and+structural+growth.
2017 A G protein-coupled α7 nicotinic receptor regulates signaling and TNF-α release in microglia. King , J. R.,Gillevet , T.C.,Kabbani , N. FEBS Open Bio 7(9) 1350-1361. http://doi.org/10.1002/2211-5463.12270 Acetylcholine activation of α7 nicotinic acetylcholine receptors (α7 nAChRs) in microglia attenuates neuroinflammation and regulates TNF-α release. We used lipopolysaccharide to model inflammation in the microglial cell line EOC20 and examined signaling by the α7 nAChR. Co-immunoprecipitation experiments confirm that α7 nAChRs bind heterotrimeric G proteins in EOC20 cells. Interaction with Gαi mediates α7 nAChR signaling via enhanced intracellular calcium release and a decrease in cAMP, p38 phosphorylation, and TNF-α release. These α7 nAChR effects were blocked by the inhibition of Gαi signaling via pertussis toxin, PLC activity with U73122, and α7 nAChR channel activity with the selective antagonist α-bungarotoxin. Moreover, α7 nAChR signaling in EOC20 cells was significantly diminished by the expression of a dominant-negative α7 nAChR, α7345-8A, shown to be impaired in G protein binding. These findings indicate an essential role for G protein coupling in α7 nAChR function in microglia leading to the regulation of inflammation in the nervous system. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=A+G+protein-coupled+%CE%B17+nicotinic+receptor+regulates+signaling+and+TNF-%CE%B1+release+in+microglia.
2018 Alpha 7 nicotinic receptors attenuate neurite development through calcium activation of calpain at the growth cone. King , J. R.,Kabbani , N. PLoS ONE 13(5) e0197247. http://doi.org/10.1371/journal.pone.0197247 The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth. α7 nAChR mediated EB3 comet motility, spectrin breakdown, and neurite growth was also inhibited by the addition of the selective calpain blocker calpeptin and attenuated by the expression of an α7 subunit unable to bind Gαq and activate calcium store release. The findings indicate that α7 nAChRs regulate cytoskeletal dynamics through local calcium signals for calpain protease activity. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Alpha+7+nicotinic+receptors+attenuate+neurite+development+through+calcium+activation+of+calpain+at+the+growth+cone.
2007 State statutes governing direct shipment of alcoholic beverages to consumers: precedents for regulating tobacco retail shipments (pp. I-1 to I-26). Kinney , L.F., , In R.J. Bonnie K. Stratton R.B. Wallace (Eds.). IOM (Institute of Medicine): Ending the Tobacco Problem: A Blueprint for the Nation. Washington DC: The National Academies Press.
2017 Behavioral healthcare staff attitudes and practices regarding consumer tobacco cessation services. Koch , J.R.,Breland , A.B. Journal of Behavioral Health Services & Research 44(3) 399-413 Given the high prevalence of tobacco use among persons with behavioral health disorders, there has been much discussion about if and when tobacco cessation services should be provided to consumers. Approximately 1700 staff (who served adults and youth) from 38 public behavioral healthcare agencies in Virginia completed a survey on their attitudes and practices regarding tobacco cessation services for consumers. Results showed that most staff (88%) think tobacco cessation services should be offered and do not interfere with treatment. Most staff (57%) always/usually screened consumers for tobacco use, but few (14%) always/usually provided tobacco cessation counseling. Reported barriers included consumers not wanting to quit and a lack of staff training. Most staff reported that their organizations do not have policies regarding tobacco cessation services. Use of tobacco cessation practices was related to staff confidence using the practices, preparedness, and years of experience. Steps to improving the use of tobacco cessation practices in this setting are discussed. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Behavioral+healthcare+staff+attitudes+and+practices+regarding+consumer+tobacco+cessation+services.
2011 Exploring behavioral and molecular mechanisms of nicotine reward in adolescent mice. Kota , D.,Sanjakdar , S.,Marks , M. J.,Khabour , O.,Alzoubi , K.,Damaj , M.I. Biochemical pharmacology 82(8) 1008-1014 Tobacco smoking during adolescence has become a prominent preventable health problem faced in the United States. Addictive properties of smoking are thought to have a pronounced effect at a young age, thereby increasing vulnerability to a life-long addiction and decreasing the likelihood of smoking cessation during adulthood. Learning and memory involvement in nicotine reward was assessed in early adolescent (PND 28-34) and adult (PND 70+) male ICR mice by conducting conditioning sessions of nicotine (0.5mg/kg) acquisition at varying time-spans, and evaluating extinction and reinstatement of nicotine preference using Conditioned Place Preference. Acquisition studies resulted in a significant preference for nicotine after 3 days of conditioning for both age groups, but not after only 1 or 2 conditioning days. In the extinction study, adolescent mice exhibited preference for nicotine 72 h after the last conditioning session, whereas preference for nicotine was extinct in adult mice by 72 h. Reinstatement studies showed adolescent mice, but not adult mice, recovering nicotine preference after a priming injection of 0.1mg/kg nicotine on day 9 after the mice underwent extinction. No significant differences were found when nAChRs were quantified in both early adolescent and adult mice using binding techniques including cytisine sensitive, α-conotoxin-MII sensitive, and α-bungarotoxin sensitive nAChRs. Levels of striatal dopamine release were measured in both age groups using a dopamine release assay over a range of nicotine doses, which also resulted in no significant differences. More sensitive assays may facilitate in understanding the mechanisms of nicotine reward in adolescent mice. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/21708139
2007 Nicotine dependence and reward differ between adolescent and adult male mice. Kota , D.,Martin , B.R.,Robinson , S.E.,Damaj , M.I. J Pharmacol Exp Ther 322(1) 399-407 The present study defined age differences in several aspects of nicotine dependence using male mice of two age groups [postnatal day (PND) 28 and PND 70]. Adolescent and adult mice displayed differences in acute sensitivity to nicotine, rewarding and withdrawal effects, development of tolerance to nicotine, and nicotinic receptor function. In the condition place preference model, adolescent mice displayed a higher sensitivity to nicotine than adults. In addition, in spontaneous and mecamylamine-precipitated withdrawal models, adolescent mice displayed fewer withdrawal signs than adults. In response to acute nicotine, it was found that adolescent mice displayed greater nicotine-induced antinociception compared with adult counterparts in the tail-flick test. Furthermore, differences in tolerance to nicotine were also noted in that adolescents developed a significantly higher degree of tolerance to nicotine in the hot-plate test compared with adults. Finally, using rubidium efflux assays, it was found that adolescent nicotinic receptors in different brain areas displayed significantly increased functionality compared with adult receptors. These data indicate that the underlying receptor mechanisms of nicotine dependence differ for adults and adolescents, suggesting that the effectiveness of smoking cessation therapies will differ for various age groups. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/17446302
2009 Enhanced Nicotine Reward in Adulthood After Exposure to Nicotine During Early Adolescence in Mice. Kota , D.,Robinson , S.E.,Damaj , M.I. Biochemical Pharmacology 78(7) 873-9 Approximately one million adolescents begin smoking cigarettes every year. Studies show that adolescents may be particularly vulnerable to various aspects of nicotine dependence. Work on rodents demonstrates parallel findings showing that adolescence is a time of changed sensitivity to both rewarding and aversive effects of nicotine. However, it is unclear if these effects are long-lasting and whether they contribute to a lifetime of nicotine addiction. In this study we have characterized the effects of adolescent nicotine exposure on the rewarding properties of nicotine in adulthood using the CPP model. Specifically, we have addressed whether the phase of adolescence (early, middle, or late adolescence) plays a role in the susceptibility to the enhanced rewarding effects of nicotine. Furthermore, we have investigated the long-term effects of adolescent nicotine exposure on nicotine reward in adulthood and have correlated these behavioral adaptations with possible molecular mechanisms. We observed that early adolescence in the mouse is a unique phase for elevated sensitivity to nicotine reward using a CPP model. In addition, exposure to nicotine during this phase, but not during late adolescence or adulthood, resulted in a lasting enhancement of reward in adulthood. Finally, we have shown that early adolescent nicotine exposure significantly elevates nAChR function in adulthood. Overall, we demonstrate that early adolescence represents a period of development, distinct from middle and late adolescence, during which nicotine exposure can cause persistent changes in behavior and molecular adaptations. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/19576867
2008 Age-dependent differences in nicotine reward and withdrawal in female mice. Kota , D.,Martin , B.R.,Damaj , M.I. Psychopharmacology 198(2) 201-10 RATIONALE: Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female. OBJECTIVE: The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence. MATERIALS AND METHODS: Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined. RESULTS: In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature. CONCLUSIONS: These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/18338157
2012 Evolving public health nursing roles: Focus on community participatory health promotion and prevention. Kulbok , P. A.,Thatcher , E.,Park , E.,Meszaros , P.S. OJIN: The Online Journal of Issues in Nursing 17(2) 1 Public health nursing (PHN) practice is population-focused and requires unique knowledge, competencies, and skills. Early public health nursing roles extended beyond sick care to encompass advocacy, community organizing, health education, and political and social reform. Likewise, contemporary public health nurses practice in collaboration with agencies and community members. The purpose of this article is to examine evolving PHN roles that address complex, multi-causal, community problems. A brief background and history of this role introduces an explanation of the community participation health promotion model. A community-based participatory research project, Youth Substance Use Prevention in a Rural County provides an exemplar for description of evolving PHN roles focused on community health promotion and prevention. Also included is discussion about specific competencies for PHNs in community participatory health promoting roles and the contemporary PHN role. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/22686109
2008 Factors influencing adolescents' decision not to smoke. Kulbok , P.A.,Rhee , H.,Botchwey , N.,Hinton , I.,Bovbjerg , V.,Anderson , N.L. Public Health Nursing. 25(6) 505-15 OBJECTIVE: Although adolescents ultimately make their own decisions to smoke or not to smoke, social, economic, and environmental circumstances shape their choices. Most research on prevention of youth tobacco use focuses on predictors of smoking initiation. In this study, we explored nonsmoking attitudes, beliefs, and norms from the perspective of 16-17-year-old nonsmokers. DESIGN: This qualitative study targeted nonsmoking youths because most social policy in the arena of tobacco prevention aims to support adolescents who are tobacco free. SAMPLE: Participants were 39 nonsmokers recruited from youth organizations in an urban community and included 22 African Americans (12 females; 10 males) and 17 Caucasian Americans (10 females; 7 males). METHODS: A health behavior framework guided the development of semistructured questions on attitudes, beliefs, and norms associated with nonsmoking, used in eight in-depth group interviews. RESULTS: Concerns for health and addiction, a positive self-image, and perceived confidence, emerged as factors affecting participants' decisions not to smoke. The approval of parents and friends, and personal beliefs further reinforced adolescents' nonsmoking decisions. CONCLUSIONS: There were more commonalities than differences in nonsmoking attitudes across gender and race. Future studies of youth tobacco prevention should employ multifaceted approaches targeting adolescents' attitudes, families, and peer networks. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/18950415
2012 Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay. Locklear , L. L.,McDonald , C.G.,Smith , R. F.,Fryxell , K.J. Neuropharmacology 63(4) 582-592 Nicotine has both rewarding and aversive properties in rodents, as shown by intravenous self-administration, intracranial self-stimulation, and conditioned place preference experiments. However, high throughput models of nicotine reward have not been developed in mice. In previous two-bottle studies, mice often chose to drink less from the nicotine bottle than from the water bottle, which raises the question whether these paradigms provide a model of the reinforcing properties of oral nicotine. We hypothesized that previous two-bottle choice paradigms included factors (such as the brief duration of trials, the addition of flavorings to both bottles, water bottles located relatively close to each other, etc.) that may have obstructed the formation of a learned association between the taste of nicotine and its delayed pharmacological effects. Here we show that a paradigm designed to simplify the acquisition of a learned association resulted in nicotine consumption by various strains and sexes that diverged progressively over a period of seven weeks. The strain and sex with the highest nicotine consumption (C57BL/6J females) showed steady and statistically significant increases in nicotine consumption throughout this period. C57BL/6J females were clearly responding to the reinforcing properties of nicotine because they chose to drink over 70% of their fluids from the nicotine bottle. Moreover, they became nicotine dependent, as shown by highly significant nicotine withdrawal symptoms after the nicotine bottle was removed. The strain and sex with the lowest consumption (A/J males) showed a significant decrease in nicotine consumption, and by the end of the experiment were drinking only 24% of their fluids from the nicotine bottle. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/22583831
2013 Exercise as a novel treatment for drug addiction: A neurobiological and stage-dependent hypothesis. Lynch , W. J.,Peterson , A.B.,Sanchez , V.,Abel , J.,Smith , M.A. Neuroscience & Biobehavioral Reviews. 37(8) 1622-44 Physical activity, and specifically exercise, has been suggested as a potential treatment for drug addiction. In this review, we discuss clinical and preclinical evidence for the efficacy of exercise at different phases of the addiction process. Potential neurobiological mechanisms are also discussed focusing on interactions with dopaminergic and glutamatergic signaling and chromatin remodeling in the reward pathway. While exercise generally produces an efficacious response, certain exercise conditions may be either ineffective or lead to detrimental effects depending on the level/type/timing of exercise exposure, the stage of addiction, the drug involved, and the subject population. During drug use initiation and withdrawal, its efficacy may be related to its ability to facilitate dopaminergic transmission, and once addiction develops, its efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with brain-derived neurotrophic factor (BDNF) in the reward pathway. We conclude with future directions, including the development of exercise-based interventions alone or as an adjunct to other strategies for treating drug addiction. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/23806439
2017 Exercise or saccharin during abstinence block estrus-induced increases in nicotine-seeking. Lynch , W.J.,Tan , L.,Narmeen , S.,Beiter , R.,Brunzell , D.H. Physiology & Behavior. [Epub ahead of print]
2010 Role of progesterone in nicotine addiction: evidence from initiation to relapse. Lynch , W. J.,Sofuoglu , M. Experimental and clinical psychopharmacology 18(6) 451 Nicotine addiction continues to be the main cause of preventable death in developed countries. Women and teen girls appear to be more vulnerable on certain aspects of nicotine addiction compared with men and boys. While the mechanism of gender differences in nicotine addiction is not yet clear, evidence suggests that while estrogen may underlie enhanced vulnerability in females, progesterone may protect females. Thus, progesterone may have therapeutic use for tobacco addiction, especially in female smokers. A greater understanding of the role of progesterone in nicotine addiction is important not only from a treatment standpoint, but also from a prevention standpoint: hormone transition phases, such as those that occur at adolescence, and during pregnancy and following birth, as well as following hormonal manipulation (e.g., using methods of hormonal birth control), may all contribute to changes in vulnerability to nicotine addiction. In this review, we summarize recent evidence from clinical and preclinical studies examining the role of progesterone in nicotine addiction focusing on its role during initiation of use and during later phases of the addiction process as a potential relapse prevention treatment. We conclude with future directions including further examination of progesterone as a potential intervention and treatment of nicotine addiction. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/21186920
2009 Sex and Ovarian Hormones Influence Vulnerability and Motivation For Nicotine During Adolescence in Rats. Lynch , W.J., , Pharmacology Biochemistry and Behavior 94(1) 43�50 The purpose of this study was to examine sex differences in sensitivity to nicotine's reinforcing effects during adolescence, a hormone transition phase characterized by rapid and marked changes in levels of gonadal hormones. Male and female rats were trained to self-administer nicotine (5 or 10 microg/kg/infusion) under a fixed-ratio 1 schedule beginning on postnatal day 30. Following acquisition, responding was assessed under a progressive-ratio schedule until postnatal day 45 with blood sampling occurring prior to the first 5 sessions in order to determine the relationship between gonadal hormones (i.e., estradiol and progesterone in females and testosterone in males) and responding for nicotine. Under low dose conditions, a greater percentage of females than males acquired nicotine self-administration. Under progressive-ratio testing conditions, although adolescent females and males initially responded at similar levels, by the end of the adolescent testing period, females responded at higher levels than males to obtain nicotine infusions. Levels of responding under the progressive-ratio schedule were negatively associated with progesterone and positively associated with the ratio of estradiol to progesterone. These findings demonstrate an enhanced sensitivity in adolescent females as compared to adolescent males to nicotine's reinforcing effects with evidence implicating circulating hormone levels as modulating this sensitivity. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/19619575
2004 A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence. Maes , H.H.,Sullivan , P.F.,Bulik , C.M.,Neale , M.C.,Prescott , C.A.,Eaves , L.J.,Kendler , K.S. Psychological Medicine Psychological Medicine 34(7) 1251-61 BACKGROUND: Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary. METHOD: We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry. RESULTS: The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80 % of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75 %, 80 % and 60 % respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females. CONCLUSIONS: This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/15697051
2015 Development and outcomes of a text messaging tobacco cessation intervention with urban adolescents. Mason , M.,Campbell , L.,Way , T.,Keyser-Marcus , L.,Benotsch , E.,Mennis , J.,Zhang , J.,King , L.,May , J.,Stembridge , D.R. Substance Abuse 36(4) 500-506 BACKGROUND: This paper describes the development of an urban adolescent text messaging tobacco cessation intervention and preliminary findings from a randomized, controlled trial. The authors successfully adapted a face-to-face intervention into a personalized, automated, and interactive 5-day texting protocol. METHODS: Respondent-driven sampling was used beginning at a community substance abuse facility. Seventy-two tobacco-dependent adolescents were randomized into an automated computer texting program that delivered either the experimental condition of 30 motivational interviewing- and social network counseling-based personalized messages or the attention control condition consisting of a texting program covering general (non-smoking-related) health habits. All teens were provided smartphones for the study and were assessed at baseline and at 1, 3, and 6 months post intervention. Analyses examined condition×time interactions. RESULTS: At 6 months, the experimental condition decreased the number of cigarettes smoked in the past 30 days, increased intentions not to smoke in the future, and increased peer social support compared with controls. Effect sizes were moderate to large. CONCLUSIONS: These findings are unique, as they target urban adolescents with a mobile health format and add to the growing literature on the efficacy of text-delivered interventions. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Development+and+outcomes+of+a+text+messaging+tobacco+cessation+intervention+with+urban+adolescents.
2015 Real-time readiness to quit and peer smoking within a text message intervention for adolescent smokers: Modeling mechanisms of change. Mason , M.,Mennis , J.,Way , T.,Floyd Campbell , L. Journal of Substance Abuse Treatment 59 67-73 The psychological construct, readiness to change, is established as a central construct within behavioral change theories such as motivational interviewing (MI). Less is known about the interplay of mechanisms for change within adolescent treatment populations. Understanding the timing and interactive influence that adolescents' readiness to stop smoking and peer smoking have on subsequent tobacco use is important to advance intervention research. Toward this end, we used ecological momentary assessment (EMA) data from an automated texting smoking intervention randomized controlled trial to model the interactive effects of readiness to stop smoking and friends smoking on adolescent tobacco use. Two hundred adolescents were randomized into experimental treatment or attention control conditions, provided smart phones, and were followed for 6 months. African American youth represented the majority of the sample. We collected monthly EMA data for 6 months on friends smoking and readiness to stop smoking as well as survey outcome data. We tested a moderated mediation model using bias corrected bootstrapping to determine if the indirect effect of treatment on cigarettes smoked through readiness to stop smoking was moderated by friends smoking. Findings revealed that readiness to stop smoking mediated the effects of treatment on cigarettes smoked for those adolescents with fewer friends smoking, but not for those with more friends smoking. These results support importance of peer-focused interventions with urban adolescents and provide target mechanisms for future research. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Real-time+readiness+to+quit+and+peer+smoking+within+a+text+message+intervention+for+adolescent+smokers%3A+Modeling+mechanisms+of+change.
2015 Time-varying effects of a text-based smoking cessation intervention for urban adolescents. Mason , M.,Mennis , J.,Way , T.,Lanza , S.,Russel , M.,Zaharakis , N. Drug and Alcohol Dependence 157 99-105 INTRODUCTION: Craving to smoke is understood as an important mechanism for continued smoking behavior. Identifying how smoking interventions operate on craving with particular populations is critical for advancing intervention science. This study's objective was to investigate the time-varying effect of a text-delivered smoking cessation intervention. METHODS: Toward this end, we used ecological momentary assessment (EMA) data collected from a five-day, automated text-messaging smoking cessation randomized clinical trial with 200 urban adolescents. We employed a time-varying effect model (TVEM) to estimate the effects of stress (time-varying covariate) and baseline nicotine dependence level (time-invariant covariate) on craving over six months by treatment condition. The TVEM approach models behavioral change and associations of coefficients expressed dynamically and graphically represented as smooth functions of time. RESULTS: Controlling for gender, age, and current smoking, differences in trajectories of craving between intervention and control conditions were apparent over the course of the study. During months 2 to 3, the association between stress and craving was significantly stronger among the control group, suggesting treatment dampens this association during this time period. The intervention also reduced the salience of baseline dependence among treatment adolescents, with craving being reduced steadily over time, while the control group increased craving over time. CONCLUSIONS: These results provide insight into the time-varying nature of treatment effects for adolescents receiving a text-based smoking cessation intervention. The ability to specify when in the course of an intervention the effect is strongest is important in developing targeted and adaptive interventions that can adjust strategically with time. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/26507175
2016 Text message delivered peer network counseling for adolescent smokers: A randomized clinical trial. Mason , M.,Mennis , J.,Way , T.,Zaharakis , N.,Campbell , L.F.,Benotsch , E.,Keyser-Marcus , L.,King , L. The Journal of Primary Prevention 37(5) 403-420 Although adolescent tobacco use has declined in the last 10 years, African American high school seniors' past 30-day use has increased by 12 %, and as they age they are more likely to report lifetime use of tobacco. Very few urban youth are enrolled in evidenced-based smoking prevention and cessation programming. Therefore, we tested a text messaging smoking cessation intervention designed to engage urban youth through an automated texting program utilizing motivational interviewing-based peer network counseling. We recruited 200 adolescents (90.5 % African American) into a randomized controlled trial that delivered either the experimental intervention of 30 personalized motivational interviewing-based peer network counseling messages, or the attention control intervention, consisting of text messages covering general (non-smoking related) health habits. All adolescents were provided smart phones for the study and were assessed at baseline, and at 1, 3, and 6 months post intervention. Utilizing repeated measures general linear models we examined the effects of the intervention while controlling for race, gender, age, presence of a smoker in the home, and mental health counseling. At 6 months, participants in the experimental condition significantly decreased the number of days they smoked cigarettes and the number of cigarettes they smoked per day; they significantly increased their intentions not to smoke in the future; and significantly increased peer social support among girls. For boys, participants in the experimental condition significantly reduced the number of close friends in their networks who smoke daily compared to those in the control condition. Effect sizes ranged from small to large. These results provide encouraging evidence of the efficacy of text messaging interventions to reduce smoking among adolescents and our intervention holds promise as a large-scale public health preventive intervention platform. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Text+message+delivered+peer+network+counseling+for+adolescent+smokers%3A+A+randomized+clinical+trial.
2016 The dynamic role of urban neighborhood effects in a text-messaging adolescent smoking intervention. Mason , M.,Mennis , J.,Zaharakis , N.,Way , T. Nicotine and Tobacco Research 18(5) 1039-1045 INTRODUCTION: Neighborhood features such as the density of tobacco outlets relative to one's home and evaluations of safety of one's activity space (routine locations), are known to influence health behaviors. Understanding the time-varying nature of these aspects of the urban ecology provides unique insights into the dynamic interactions of individuals and their environments. METHODS: The present study tested the time-varying effects of tobacco outlets and perceived safety within a randomized controlled trial of an adolescent text-messaging smoking intervention. We used ecological momentary assessment data (EMA) from an automated text-messaging smoking cessation randomized trial with 197 primarily African American urban adolescents. We employed a time-varying effect model to estimate the effects of density of tobacco outlets within one-half mile of participants' home locations (time-invariant covariate) and evaluations of safety of their activity space (time-varying covariate) on momentary smoking over 6 months by treatment condition. The time-varying effect model approach models behavioral change and associations of coefficients expressed dynamically and graphically represented as smooth functions of time. RESULTS: Differences in trajectories of smoking between treatment conditions were apparent over the course of the study. During months 2 and 6, the association between tobacco outlet density and smoking was significantly stronger in the control condition, suggesting treatment dampens this association during these time periods. The intervention also significantly reduced the association of perceived safety and smoking among the treatment condition during months 3 through 6. CONCLUSIONS: Results support testing the time-varying effects of urban ecological features and perceptions of safety among adolescents in text-based smoking cessation interventions. IMPLICATIONS: This study makes a unique contribution towards understanding the time-varying effects of urban neighborhoods on adolescent tobacco use within the context of a text-delivered intervention. Helping to adjust the long-held conceptualization of intervention effects as a static outcome, to that of a dynamic, time-varying process, is an important contribution of this study. The ability to specify when behavioral change occurs within the context of a randomized control trial provides understanding into the time-varying treatment effects of text-based smoking intervention. For example, researchers can modify the intervention to have strategically timed booster sessions that align with when the odds of smoking begin to increase in order to provide more precise treatment. The current study results show that increasing support to participants during months 2 and 4 may help suppress smoking over the course of a 6-month intervention. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=The+dynamic+role+of+urban+neighborhood+effects+in+a+text-messaging+adolescent+smoking+intervention.
2004 Influences on Adolescent Girls' Decisions Not to Smoke Cigarettes: Results from a Qualitative Study. In P. Meszaros, F. Piercy, A. Huebner, H. Crawford, K. Castagnoli. (Eds.). Adolescent Females & Smoking. Matheson , J.L.,Meszaros , P. Monograph published by the Center for Information Technology Impacts on Children Youth and Families. Blacksburg VA: Virginia Tech.
2004 Cigarette smoking among adolescent females. Matheson , J.L.,Meszaros , P.,Huebner , A.,Piercy , F.,Davis , S.,Shettler , L. In P. Meszaros F. Piercy A. Huebner H. Crawford K. Castagnoli. (Eds.). Adolescent Females & Smoking. Monograph published by the Center for Information Technology Impacts on Children Youth and Families. Blacksburg VA: Virginia Tech. Virginia Tech
2005 Periadolescent nicotine administration produces enduring changes in dendritic morphology of medium spiny neurons from nucleus accumbens. McDonald , C.G.,Dailey , V.K.,Bergstrom , H.C.,Wheeler , T.L.,Eppolito , A.K.,Smith , L.N.,Smith , R.F. Neuroscience Letters 385 163-167 The objective of the current study was to examine how periadolescent nicotine exposure affects dendritic morphology of medium spiny neurons from the nucleus accumbens shell. Male Long-Evans hooded rats were chronically administered nicotine or saline for a period extending from postnatal day 22 (p22) to p69. Nicotine and saline administration was via subcutaneously implanted osmotic pumps. At p144, 75 days after conclusion of nicotine administration, brains were processed for Golgi-Cox staining. Medium spiny neurons from the nucleus accumbens shell were digitally reconstructed. It was found that neurons from nicotine-treated animals possessed significantly longer dendrites and a greater number of dendritic segments than control animals. A branch order analysis indicated that differences in dendritic length and segment number were most pronounced in third and fourth order segments. A subsequent behavioral experiment suggests that the observed anatomical changes are associated with enduring psychomotor differences. These findings indicate that periadolescent exposure to nicotine can result in long-lasting structural changes in the nucleus accumbens shell and are consistent with behavioral data suggesting that adolescent nicotine exposure may result in vulnerability to nicotine addiction in adulthood. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/15955627
2007 Evidence for elevated nicotine-induced structural plasticity in nucleus accumbens of adolescent rats. McDonald , C.G.,Eppolito , A.K.,Brielmaier , J.M.,Smith , L.N.,Bergstrom , H.C.,Lawhead , M.R.,Smith , R.F. Brain Research 1151 211-218 Male Long-Evans rats were administered nicotine bitartrate or sodium tartrate either during adolescence (p29-43) or adulthood (p80-94). Route of administration was via subcutaneously implanted osmotic pump (initial dose 2.0 mg/kg/day, free base). Five weeks following nicotine administration, brains were processed for Golgi-Cox staining. Medium spiny neurons from nucleus accumbens (NAc) shell were digitally reconstructed for morphometric analysis. Total dendritic length and branch number were greater in medium spiny neurons from animals pretreated with nicotine during adolescence. A branch order analysis indicated that increased branch number was specific to higher order branches. Mean branch lengths did not differ with respect to treatment as a function of branch order. Thus, nicotine-induced increases in total dendritic length were a function of greater numbers of branches, not increased segment length. In contrast, adult nicotine exposure did not significantly alter total dendritic length or branch number of medium spiny neurons. Total dendritic length and branch number of a second morphological type, the large aspiny neuron, did not differ following either adolescent or adult pretreatment. The age-dependent alteration of accumbal structure was associated with qualitatively different behavioral responses to drug challenge. These data provide evidence that drug-induced structural plasticity in nucleus accumbens is considerably more pronounced during adolescence. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/?term=Evidence+for+elevated+nicotine-induced+structural+plasticity+in+nucleus+accumbens+of+adolescent+rats.
2016 Tobacco outlet density and attitudes towards smoking among urban adolescent smokers. Mennis , J.,Mason , M. Substance Abuse in press. 37(4) 521-525 BACKGROUND: This study investigates whether residential exposure to tobacco outlets (i.e., convenience stores and other stores selling tobacco) is associated with attitudes towards smoking among a sample of urban, primarily African American, adolescent smokers. METHODS: Cross-sectional survey data for 197 adolescents were integrated with spatial data on tobacco outlets via subject home addresses. Ordinal regression was employed to test hypotheses that closer proximity to, and higher concentrations of, tobacco outlets are associated with higher measures of intention to continue to smoke in the future, weaker self-efficacy related to stopping smoking, and more accepting social norms related to smoking, while controlling for characteristics of age, gender, family and peer smoking contexts, and level of nicotine dependence. Moderation by age and gender was also investigated. RESULTS: Higher residential tobacco outlet density is significantly associated with a greater intention to smoke in the next 3 months, a lower readiness to stop smoking, and a greater likelihood of accepting a cigarette from a friend. Residential proximity to a tobacco outlet is significantly associated with a greater intention to smoke 5 years on. Evidence of a relationship between exposure to tobacco outlets and social norms related to smoking was not found, nor was there evidence for moderation of these relationships by age or gender. CONCLUSIONS: These results suggest that among urban adolescents who currently smoke, higher residential exposure to tobacco outlets is associated with greater predisposition towards future smoking and lower self-evaluation of the ability to stop smoking. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/27171155
2016 The role of tobacco outlet density in a smoking cessation intervention for urban youth. Mennis , J.,Mason , M.,Way , T.,Zahakaris , N. Health & Place 38 39-47 This study investigates the role of tobacco outlet density in a randomized controlled trial of a text messaging-based smoking cessation intervention conducted among a sample of 187 primarily African American youth in a midsize U.S. city. A moderated mediation model was used to test whether the indirect effect of residential tobacco outlet density on future smoking was mediated by the intention to smoke, and whether this indirect effect differed between adolescents who received the intervention and those who did not. Results indicated that tobacco outlet density is associated with intention to smoke, which predicts future smoking, and that the indirect effect of tobacco outlet density on future smoking is moderated by the intervention. Tobacco outlet density and the intervention can be viewed as competing forces on future smoking behavior, where higher tobacco outlet density acts to mitigate the sensitivity of an adolescent to the intervention's intended effect. Smoking cessation interventions applied to youth should consider tobacco outlet density as a contextual condition that can influence treatment outcomes. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/26798960
2004 Effective smoking prevention and cessation programs for adolescent girls: a proposed framework for program design. In P. Meszaros, F. Piercy, A. Huebner, H. Crawford, K. Castagnoli. (Eds.). Meszaros , P.,Matheson , J.L.,Huebner , A.,Piercy , F.,Davis , S.,Shettler , L. Adolescent Females & Smoking. Monograph published by the Center for Information Technology Impacts on Children Youth and Families. Blacksburg VA: Virginia Tech. This paper focuses on the current internationally published literature on adolescent girls smoking prevention and cessation programs. Published literature on prevention and cessation programs that have been developed for and used with girls, especially those with published effectiveness data are reviewed separately. Using relevant literature and the results of a recent Delphi Study identifying program components experts cited as most effective for female smoking prevention, a human ecological framework for designing programs for female adolescents will be proposed. Areas for further research will also be identified. Virginia Tech
2014 How to freak a Black & Mild: a multi-study analysis of YouTube videos illustrating cigar product modification. Nasim , A.,Blank , M.D.,Cobb , C. O.,Berry , B.M.,Kennedy , M.G.,Eissenberg , T. Health Education Research 29(1) 41-57 Cigar smoking is increasingly common among adolescents who perceive cigars as less harmful than cigarettes. This perception of reduced harm is especially true for cigars that are user-modified by removing the tobacco binder through a process called 'freaking'. Little is known about 'freaking' and this multi-study, mixed-methods analysis sought to understand better the rationale and prevailing beliefs about this smoking practice using YouTube videos. In Study 1, we conducted a descriptive content analysis on the characteristics of 26 randomly sampled cigar product modification (CPM) videos posted during 2006-10. In Study 2, a thematic analysis was performed on the transcripts of commentary associated with each video to characterize viewers' comments about video content. Study 1 results revealed that 90% of videos illustrated a four-step CPM technique: 'Loosening the tobacco'; 'Dumping the tobacco'; 'Removing the cigar binder' and 'Repacking the tobacco'. Four themes related to the purpose of CPM were also derived from video content: 'Easier to smoke' (54%), 'Beliefs in reduction of health risks' (31%), 'Changing the burn rate' (15%) and 'Taste enhancement' (12%). Study 2 results concerning the content characteristics of video comments were categorized into three themes: 'Disseminating information/answering questions' (81%), 'Seeking advice/asking questions' (69%) and 'Learning cigar modification techniques' (35%). Favorable comments were more common (81%) compared to unfavorable (58%) and comment content suggested low-risk perceptions and poor understanding of smoking harms. These findings highlight a novel means for youth to access information concerning CPM that may have important implications for tobacco control policy and prevention. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/24162926
2013 A multiple indicators and multiple causes model of alternative tobacco use. Nasim , A.,Blank , M.D.,Cobb , C. O.,Eissenberg , T. American Journal of Health Behavior 37(1) 25-31 OBJECTIVE: To examine the relationship between adolescents' cigarette smoking experiences and alternative tobacco product (ATP) use. METHODS: Multiple indicators and multiple causes (MIMIC) models estimated simultaneously the relationship between cigarette smoking experiences and ATP use among high school students (N=1827) completing the 2009 Virginia Youth Tobacco Survey. RESULTS: Overall, ATP use was associated with adolescents' ever use of cigarettes, early onset of cigarette smoking, cigarettes smoked per day, and peer smoking; however, important model differences between racial/ethnic groups were observed. CONCLUSIONS: Prevention and cessation programs might reduce adolescent ATP use by targeting specific characteristics of cigarette smoking. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/22943098
2012 Trends in alternative tobacco use among light, moderate, and heavy smokers in adolescence, 1999-2009. Nasim , A.,Khader , Y.,Blank , M. D.,Cobb , C.O.,Eissenberg , T. Addictive Behaviors 37(7) 866-870 OBJECTIVE: To examine trends in alternative tobacco product (ATP) use (smokeless tobacco, cigars, and bidis/cloves) among a national sample of adolescent cigarette smokers (light, moderate, and heavy) during 1999-2009. METHOD: A secondary analysis of data from the 1999-2009 National Youth Tobacco Survey was performed to investigate the tobacco behaviors of 6th through 12th graders enrolled in public and private schools in the United States. Long-term trends in ATP use were analyzed using logistic regression--controlling for sex, grade, and race/ethnicity--and simultaneously assessing linear and higher order time effects and their interaction with cigarette smoking status. RESULTS: During 1999-2009, increases in smokeless tobacco use and decreases in bidis/cloves use were observed across all smoking groups. For cigars, declines were observed for heavy and moderate smokers, but levels returned to baseline levels in 2009. Cigar use among light smokers was less variable. Rates of any ATP were highest among heavy smokers and lowest among light smokers. CONCLUSION: Trends in cigarette and SLT use increased dramatically in the past decade, and this increase is evident across all cigarette smoker types. Implications for tobacco surveillance, prevention and cessation programs, and tobacco control policies are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Trends+in+alternative+tobacco+use+among+light%2C+moderate%2C+and+heavy+smokers+in+adolescence%2C+1999-2009.
2012 Cigar use misreporting among youth: Data from the 2009 Youth Tobacco Survey, Virginia. Nasim , A.,Blank , M.D.,Berry , B. M.,Eissenberg , T. Preventing chronic disease 9 INTRODUCTION: Researchers have suggested that adolescents' cigar use has increased beyond the rates being reported on tobacco use surveys. Differences in content knowledge and everyday colloquial expressions may be responsible for misreporting of cigar use. To determine whether cigar use is subject to systematic misreporting, we compared reports of general cigar use ("During the past 30 days, on how many days did you smoke cigars, little cigars, and cigarillos?") with reports of brand-specific use ("During the past 30 days, on how many days did you smoke Black & Milds?") among a statewide sample of adolescents in Virginia. METHODS: We examined data from 3,093 youth who completed the 2009 Virginia Youth Tobacco Survey to determine differences in the rate of misreported cigar use (ie, those who reported Black & Mild use but did not report cigar, little cigar, or cigarillo use) for youth with varying demographic profiles and conditions. RESULTS: More than one-half of Black & Mild users (57.3%) did not report general cigar use. Cigar use misreporting was most prevalent among older adolescents, blacks/African Americans, current users of cigarettes and hookah, and youth diagnosed with asthma. CONCLUSION: General cigar-use items on statewide surveys significantly underestimate the prevalence of youth cigar use. More comprehensive measures of cigar use may be beneficial in assessing tobacco use among groups most likely to misreport their tobacco use, such as African Americans and youth diagnosed with asthma. Virginia Commonwealth University
2011 Ethnic Considerations in Risk Exposure and Cigarette Use Vulnerability among Eighth Grade Students in Virginia. Nasim , A.,Berry , B.M.,Belgrave , F. Z.,Corona , R.,Turf , E. International Quarterly of Community Health Education 31(3) 229-244 The purpose of this study was to examine risk exposure and cigarette use vulnerability among 4,559 8th grade students enrolled in Virginia public schools. The study used 2005 statewide data from the Community Youth Survey (CYS) which assessed risks and protective factors for substance use. The findings indicated that Asian youth reported the lowest exposure to community, family, school, and peer/individual risks, but were most vulnerable in terms of past 30-day cigarette use. African-American youth reported significantly greater risk exposure than did their counterparts on more than half of the risks examined; however, they were substantially less vulnerable to the effects of these risks in comparison to their White, Latino, and Asian peers. The findings are discussed with regard to prevention interventions for adolescents from different ethnic groups. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/21988869
2008 Does the source matter in the communication of anti-smoking messages to youth?. Nasim , A.,Corona , R. International quarterly of community health education 29(4) 309- 321 This study examined ethnicity as a moderator of exposure to sources of anti-smoking communication and behavioral intentions among adolescents who have never tried smoking (i.e., never smokers) and those who previously experimented with smoking but are not yet regular smokers (i.e., experimental smokers). Responses from 1700 African American, Latino, and White youth who completed the Virginia Youth Tobacco Survey from September 2007 through April 2008 were analyzed. Ethnicity and smoking status moderated the association between exposure to sources of anti-tobacco communication and adolescents' intentions to smoke. For never smokers, media exposure was related to lower behavioral intentions among African Americans. For experimental smokers, exposure to both media and to health professionals was associated with lower intentions among African Americans. Exposure to parental anti-smoking communication was associated with reduced intentions among White adolescents. These findings suggest that prevention for smoking initiation among ethnically diverse youth might be enhanced with greater attention to the source of anti-smoking messages and prior smoking experience. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/19959424
2007 . Cultural orientation as a protective factor against tobacco and marijuana smoking for African-American young women. Nasim , A.,Corona , R.,Belgrave , F.Z.,Utsey , S.O.,Fallah , N. Journal of Youth Adolescence 36 503-516 The present study examined cultural orientation as a protective factor against tobacco and marijuana smoking for African American young women (ages 18 to 25). African American college students (N=145) from a predominantly White university were administered subscales from the African American Acculturation Scale-Revised (AAAS-R); the shortened Individualism/Collectivism (INDCOL) Scale; a Tobacco and Drug Use Survey; and a background survey. Multiple logistic regression was conducted using cultural orientation variables as predictors and smoking status (i.e., tobacco and marijuana) as the criterion. It was expected that young women who endorsed traditional African American cultural characteristics (i.e., religious beliefs, health, family values, and socialization) and were collectivistic in their community (i.e., cultural interdependency) and familial (i.e., familial interdependency) interactions would be less likely to smoke. Results show that traditional religious beliefs and practice was protective against tobacco smoking for this sample of young women. Familial interdependency (e.g., supportive exchanges between friends, and consultation and sharing with parents), and traditional religious beliefs and practices surfaced as protective factors against marijuana smoking. Traditional health beliefs and practices was a risk factor for both tobacco and marijuana smoking. The implications signal the need for smoking prevention and cessation programs to focus on interpersonal factors which may strengthen African American young women's religious and familial bonding.
2006 Religiosity, refusal efficacy, and substance use among African-American adolescents and young adults. Nasim , A.,Utsey , S.O.,Corona , R.,Belgrave , F.Z. Journal of Ethnicity in Substance Abuse 5(3) 29-49
2009 Phenotypes and Endophenotypes: Foundations for Genetic Studies of Nicotine Use and Dependence. National Cancer Institute , , , Tobacco Control Monograph No. 20. U.S. Department of Health and Human Services National Institutes of Health. NIH Publication No. 09-6366. Tobacco use is the world's leading cause of preventable death. This major public health threat exists within the context of a complex interplay between genetic and environmental causes of nicotine dependence, and understanding this balance may hold the key to further reductions in the disease burden and mortality due to chronic tobacco use. This monograph explores the role of genetics in the etiology of nicotine dependence. It provides a conceptual framework for understanding nicotine dependence and for examining the usefulness of a range of potential phenotypes and endophenotypes for linking genes to behavior. This introductory part starts by summarizing the epidemiology of tobacco use, the history of genetic studies in tobacco, and the measurement of nicotine dependence. It then provides a literature review of selected biometric and genetic studies of nicotine dependence and ends with a discussion of some of the most important issues in the communication of genetic findings.
2007 Nicotine causes age dependent changes in gene expression in the adolescent female rat brain. Polesskaya , O.O.,Fryxell , K.J.,Merchant , A.D.,Locklear , L.L.,Ker , K.,McDonald , C.G.,Eppolito , A.K.,Smith , L.N.,Wheeler , T.L.,Smith , R.F. Neurotoxicology and Teratology 29 126-140 Humans often start smoking during adolescence. Recent results suggest that rodents may also be particularly vulnerable to nicotine dependence during adolescence. We examined the effect of chronic nicotine exposure on gene expression profiles during adolescence in female rats, who were dosed with nicotine (and control animals were dosed with saline) via subcutaneously implanted osmotic minipumps. Brain samples were collected at four ages: before puberty (postnatal day 25), at about the time of puberty in females (postnatal day 35), and after puberty (postnatal days 45 and 55). The expression of 7931 genes in three brain areas was measured using DNA microarrays. Quantitative RT-PCR was also employed to confirm the expression patterns of selected genes. We used a novel clustering technique (principal cluster analysis) to classify 162 nicotine-regulated genes into five clusters, of which only one (cluster A) showed similar patterns of gene expression across all three brain areas (ventral striatum, prefrontal cortex, and hippocampus). Three clusters of genes (A, B, and C) showed dramatic peaks in their nicotine responses at the same age (p35). The other two clusters (D1 and D2) showed smaller peaks and/or valleys in their nicotine responses at p35 and p45. Thus, the age of maximal gene expression response to nicotine in female rats corresponds approximately to the age of maximal behavioral response and the age of puberty. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/17234382
2007 Chronic nicotine doses down-regulate Pde4 isoforms that are targets of antidepressants in adolescent female rats. Polesskaya , O.O.,Smith , R.F.,Fryxell , K.J. Biol Psychiatry 61 56-64 BACKGROUND: Previous data in humans and animal models has suggested connections between anxiety, depression, smoking behavior, and nicotine dependence. The importance of these connections has been confirmed by clinical studies that led to the recent FDA approval of an anti-depressant (Zyban) for use in human smoking cessation programs. Other anti-depressants (such as rolipram) specifically inhibit PDE4 phosphodiesterases. METHODS: We used DNA microarrays to discover gene expression changes in adolescent female rats following chronic nicotine treatments, and real-time PCR assays to confirm and extend those results. RESULTS: We found a consistent decrease in the mRNA levels encoded by the Pde4b gene in nucleus accumbens, prefrontal cortex, and hippocampus of adolescent female rats treated with .24 mg/day nicotine, and in prefrontal cortex of adolescent female rats treated with .12 mg/day nicotine. We further show that each of these brain areas produced a different profile of Pde4b isoforms. CONCLUSIONS: Chronic nicotine treatments produce a dose-dependent down-regulation of Pde4b, which may have an antidepressant effect. This is the first report of a link between nicotine dependence and phosphodiesterase gene expression. Our results also add to the complex interrelationships between smoking and schizophrenia, because mutations in the PDE4B gene are associated with schizophrenia. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/16814262
2016 The temporal window of valuation is constricted among adolescent smokers. Quisenberry , A.J.,Bianco , A.,Gatchalian , K.M.,Kim-Spoon , J.,Bickel , W.K. Behavioural Processes 132 29-33
2015 Wheel running exercises attenuates vulnerability to self-administer nicotine in rats. Sanchez , V.,Lycas , M.D.,Lynch , W.J.,Brunzell , D.H. Drug and Alcohol Dependence 1(156) 193-198 BACKGROUND: Preventing or postponing tobacco use initiation could greatly reduce the number of tobacco-related deaths. While evidence suggests that exercise is a promising treatment for tobacco addiction, it is not clear whether exercise could prevent initial vulnerability to tobacco use. Thus, using an animal model, we examined whether exercise attenuates vulnerability to the use and reinforcing effects of nicotine, the primary addictive chemical in tobacco. METHODS: Initial vulnerability was assessed using an acquisition procedure wherein exercising (unlocked running wheel, n=10) and sedentary (locked or no wheel, n=12) male adolescent rats had access to nicotine infusions (0.01-mg/kg) during daily 21.5-h sessions beginning on postnatal day 30. Exercise/sedentary sessions (2-h/day) were conducted prior to each of the acquisition sessions. The effects of exercise on nicotine's reinforcing effects were further assessed in separate groups of exercising (unlocked wheel, n=7) and sedentary (no wheel, n=5) rats responding for nicotine under a progressive-ratio schedule with exercise/sedentary sessions (2-h/day) conducted before the daily progressive-ratio sessions. RESULTS: While high rates of acquisition of nicotine self-administration were observed among both groups of sedentary controls, acquisition was robustly attenuated in the exercise group with only 20% of exercising rats meeting the acquisition criterion within the 16-day testing period as compared to 67% of the sedentary controls. Exercise also decreased progressive-ratio responding for nicotine as compared to baseline and to sedentary controls. CONCLUSIONS: Exercise may effectively prevent the initiation of nicotine use in adolescents by reducing the reinforcing effects of nicotine. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/26433561
2013a Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats. Sanchez , V.,Moore , C.F.,Brunzell , D. H.,Lynch , W.J. Psychopharmacology 1-9 RATIONALE: Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. OBJECTIVES: The aim of this study is to determine if wheel-running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. METHODS: Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 μg/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23 h/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2 h/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. RESULTS: Intake was higher at the 10 μg/kg dose as compared to the 5 μg/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. CONCLUSIONS: Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/23371488
2013b Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model. Sanchez , V.,Moore , C.F.,Brunzell , D. H.,Lynch , W.J. Psychopharmacology 1-10 RATIONALE: Wheel running attenuates nicotine-seeking in male adolescent rats; however, it is not known if this effect extends to females. OBJECTIVE: To determine if wheel running during abstinence would differentially attenuate subsequent nicotine-seeking in male and female rats that had extended access to nicotine self-administration during adolescence. METHODS: Male (n = 49) and female (n = 43) adolescent rats self-administered saline or nicotine (5 μg/kg) under an extended access (23-h) paradigm. Following the last self-administration session, rats were moved to polycarbonate cages for an abstinence period where they either had access to a locked or unlocked running wheel for 2 h/day. Subsequently, nicotine-seeking was examined under a within-session extinction/cue-induced reinstatement paradigm. Due to low levels of nicotine-seeking in females in both wheel groups, additional groups were included that were housed without access to a running wheel during abstinence. RESULTS: Females self-administered more nicotine as compared to males; however, within males and females, intake did not differ between groups prior to wheel assignment. Compared to saline controls, males and females that self-administered nicotine showed a significant increase in drug-seeking during extinction. Wheel running during abstinence attenuated nicotine-seeking during extinction in males. In females, access to either locked or unlocked wheels attenuated nicotine-seeking during extinction. While responding was reinstated by cues in both males and females, levels were modest and not significantly affected by exercise in this adolescent-onset model. CONCLUSIONS: While wheel running reduced subsequent nicotine-seeking in males, access to a wheel, either locked or unlocked, was sufficient to suppress nicotine-seeking in females. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/24271035
2010 Adolescent nicotine exposure disrupts context conditioning in adulthood. Spaeth , A.M.,Burk , J.A.,Barnet , R.C.,Hunt , P.S. Pharmacology Biochemistry and Behavior 96(4) 501-6 Despite the prevalence of smoking among adolescents, few studies have assessed the effects of adolescent nicotine exposure on learning in adulthood. In particular, it remains unclear whether adolescent nicotine exposure has effects on hippocampus-dependent learning that persist into adulthood. The present experiment examined whether there were effects of adolescent nicotine exposure on context conditioning, a form of learning dependent on the integrity of the hippocampus, when tested during adulthood. Rats were exposed to nicotine during adolescence (postnatal days [PD] 28-42) via osmotic minipump (0, 3.0 or 6.0mg/kg/day). Context conditioning occurred in early adulthood (PD 65-70). Animals were exposed to an experimental context and were given 10 unsignaled footshocks or no shock. Additional groups were included to test the effects of adolescent nicotine on delay conditioning, a form of learning that is not dependent upon the hippocampus. Conditioning was assessed using a lick suppression paradigm. For animals in the context conditioning groups, adolescent nicotine resulted in significantly less suppression of drinking in the presence of context cues compared with vehicle-pretreated animals. For animals in the delay conditioning groups, there was a trend for adolescent nicotine (3.0mg/kg/day) to suppress drinking compared to vehicle-pretreated animals. There were no differences in extinction of contextual fear or cued fear between rats previously exposed to vehicle or nicotine. The data indicate that adolescent nicotine administration impairs context conditioning when animals are trained and tested as adults. The present data suggest that adolescent nicotine exposure may disrupt hippocampus-dependent learning when animals are tested during adulthood.
2007 Psychosocial factors associated with non-smoking adolescents' intentions to smoke. Smith , B.N.,Bean , M.K.,Mitchell , K.S.,Speizer , I.S.,Fries , E.A. Health Education Research 22(2) 238-247 Smoking is the most preventable cause of death in the United States. Most adult smokers began smoking during adolescence, making youth tobacco prevention an especially important public health goal. Guided by an extension of the theory of planned behavior (TPB), this study examined the role of psychosocial factors in accounting for adolescents' smoking intentions. Participants from three high schools (n = 785) were surveyed to assess smoking-related characteristics and behaviors as part of a statewide evaluation of tobacco prevention programming. Attitudes, subjective norms (and other normative factors) and perceived behavioral control were all associated with non-smokers' intentions to smoke. Having more favorable attitudes toward remaining tobacco free and perceiving that friends would not be supportive of smoking were both associated with decreased likelihood of intending to smoke. Normative influence and peer use were significant factors, such that having more friends who smoke was associated with increased odds of intent to smoke. Lastly, perceived difficulty to quit was related to smoking intentions, with higher confidence to quit significantly associated with intentions to smoke. Findings are consistent with the TPB--attitudes, normative factors and perceived behavioral control each helped account for non-smoking adolescents' intentions to smoke. Implications for theory and intervention building are discussed. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/16880217
2015 Adolescent nicotine alters dendritic morphology in the bed nucleus of the stria terminalis. Smith , K.C.,Ehlinger , D.G.,Smith , R.F. Neuroscience Letters 590 111-115 Adolescent nicotine increases dendritic elaboration in several areas associated with the extended amygdala. It also increases anxiety-like behavior in adulthood. An unresolved question is whether adolescent nicotine alters dendritic structure in the bed nucleus of the stria terminalis (BNST), which may contribute to altered anxiety-like behavior. To investigate this possibility, adolescent male Sprague-Dawley rats were administered nicotine (0.5 mg/kg/day) 3 days a week for 2 consecutive weeks, starting at postnatal day P (32). 17 days following the end of dosing, brains were processed for Golgi-Cox staining, and neurons were digitally reconstructed in three dimensions. Animals previously treated with nicotine exhibited an increase in the total number of branches and total length of dendrites on BNST neurons. Sholl analysis revealed an increase in the number of intersections with concentric spheres, increased amount of dendritic material within concentric spheres, and an increase of dendritic branching within concentric spheres occurring between 20 and 300 μm from the soma in dendrites. Collectively, our results show that adolescent nicotine alters dendritic structure (by triggering new branch growth), and, by inference, connectivity of the BNST, which may contribute to alterations in behavior induced by adolescent nicotine. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/25623037
2015 Role of the D3 dopamine receptor in nicotine sensitization. Smith , L.N.,Bachus , S.E.,McDonald , C.G.,Smith , R.F. Behavioural Brain Research 1(289) 92-104 Adolescent cigarette use is associated with reduced quitting success and continued smoking in adulthood. Interestingly, polymorphisms of the dopamine D3 receptor (DRD3) gene have been associated with smoking behavior, and the receptor is expressed in an age- and brain region-dependent manner that suggests relevance to addiction. Here, we investigate the possible role of dopamine-related receptors, including DRD3 and an intriguing splice variant known as D3nf, in nicotine-induced sensitization. In adolescent and adult male rats, we examined (1) alterations occurring in dopamine receptor-related mRNAs (DRD1, DRD2, DRD3 and D3nf) at two time points during a sensitizing regimen of nicotine and (2) whether DRD3 antagonism either during the initial treatment (induction) or at a later challenge exposure (expression) is able to block nicotine sensitization. Nicotine-induced changes were seen for DRD3 and D3nf mRNAs in the nucleus accumbens shell early in repeated exposure in both age groups. DRD3 antagonism only blocked the induction of sensitization in adolescents and did not block the expression of sensitization in either age group. Adolescents and adults showed opposite DRD1 mRNA responses to nicotine treatment, while no age- and nicotine-related changes in DRD2 mRNA were observed. These data reveal important age-dependent regulation of DRD1- and DRD3-related mRNAs during the course of nicotine exposure. Furthermore, they highlight a requirement for DRD3 signaling in the development of adolescent nicotine sensitization, suggesting it may represent an appropriate target in the prevention of nicotine dependence initiated at this age. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/25907750
2006 Long-term changes in fear conditioning and anxiety-like behavior following nicotine exposure in adult versus adolescent rats. Smith , L.N.,McDonald , C.G.,Bergstrom , H.C.,Brielmaier , J.M.,Eppolito , A.K.,Wheeler , T.L.,Falco , A.M.,Smith , R.F. Pharmacology Biochemistry and Behavior 85 91-97 Adolescent nicotine exposure is associated with long-term use, and it has been suggested that this vulnerability to addiction may relate to lasting anxiogenic effects of the drug. However, few studies have addressed long-term effects of adolescent nicotine, and fewer yet have compared adolescent to adult exposure. Male and female Long-Evans rats continuously received nicotine bitartrate or sodium tartrate via osmotic mini-pumps over 15 days either during adolescence (p28-42) or adulthood (p85-99). Initial nicotine dose (free base) was either low (1 mg/kg/day) or high (2 mg/kg/day). Open field behavior and fear conditioning were assessed in adulthood, 1 month post-dosing. Animals pretreated with nicotine during adolescence showed less center time in a novel open field than sham controls. Conversely, the two nicotine doses differentially affected fear conditioning. Animals pretreated with low nicotine during adolescence demonstrated superior acquisition of the task compared to sham control animals; however, unlike either high nicotine-pretreated or sham control animals, they failed to extinguish the learned behavior. In contrast, animals pretreated during adulthood did not behave significantly different from sham controls on either task. Overall, nicotine-pretreatment during adolescence induced effects on behaviors related to fear and anxiety in adulthood, while comparable pretreatment during adulthood failed to produce significant residual effects. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/16919320
2012 Exercise as a potential treatment for drug abuse: evidence from preclinical studies. Smith , M. A.,Lynch , W.J. Frontiers in Psychiatry 2 Epidemiological studies reveal that individuals who engage in regular aerobic exercise are less likely to use and abuse illicit drugs. Until recently, very few studies had examined the causal influences that mediate this relationship, and it was not clear whether exercise was effective at reducing substance use and abuse. In the past few years, several preclinical studies have revealed that exercise reduces drug self-administration in laboratory animals. These studies have revealed that exercise produces protective effects in procedures designed to model different transitional phases that occur during the development of, and recover from, a substance use disorder (e.g., acquisition, maintenance, escalation, and relapse/reinstatement of drug use). Moreover, recent studies have revealed several behavioral and neurobiological consequences of exercise that may be responsible for its protective effects in these assays. Collectively, these studies have provided convincing evidence to support the development of exercise-based interventions to reduce compulsive patterns of drug intake in clinical and at-risk populations. https://www.ncbi.nlm.nih.gov/pubmed/22347866
2015 Adolescent nicotine induces persisting changes in development of neural connectivity. Smith , R.F.,McDonald , C.G.,Bergstrom , H.C.,Ehlinger , D.G.,Brielmaier , J.M. Neuroscience and Biobehavioral Reviews 55 432-443 Adolescent nicotine induces persisting changes in development of neural connectivity. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into adulthood. Areas sensitive to, and not sensitive to, structural remodeling induced by adolescent nicotine suggest that the remodeling generally corresponds to the extended amygdala. Evidence suggests that dendritic remodeling is accompanied by persisting changes in synaptic connectivity. Modeling, electrophysiological, neurochemical, and behavioral data are consistent with the implication of our anatomical studies showing that adolescent nicotine induces persisting changes in neural connectivity. Emerging data thus suggest that early adolescence is a period when nicotine consumption, presumably mediated by nicotine-elicited changes in patterns of synaptic activity, can sculpt late brain development, with consequent effects on synaptic interconnection patterns and behavior regulation. Adolescent nicotine may induce a more addiction-prone phenotype, and the structures altered by nicotine also subserve some emotional and cognitive functions, which may also be altered. We suggest that dendritic elaboration and associated changes are mediated by activity-dependent synaptogenesis, acting in part through D1DR receptors, in a network activated by nicotine. The adolescent nicotine effects reviewed here suggest that modification of late CNS development constitutes a hazard of adolescent nicotine use. George Mason University https://www.ncbi.nlm.nih.gov/pubmed/26048001
2008 Adolescents' responses to anti-tobacco advertising: exploring the role of adolescents' smoking status and advertisement theme. Sutfin , E.L.,Szykman , L.R.,Moore , M.C. Journal of Health Communication 13(5) 480-500 Anti-smoking media directed at adolescents use many different message themes, but little evidence exists as to which is most effective. Additionally, little is known about how teens who smoke respond to anti-tobacco ads. This study examined smoking and nonsmoking adolescents' responses to three popular thematic approaches: (1) endangering others, (2) negative life circumstances, and (3) industry manipulation. Sixteen groups of high school students (total N=488) were randomly assigned in a balanced fashion to one of three anti-tobacco ad conditions or a control condition. Outcome variables included adolescents' immediate emotional and cognitive responses, and intentions to smoke. Adolescents exposed to negative life circumstances ads reported lower intentions to smoke than those exposed to control and industry manipulation ads. Additionally, adolescents' responses differed based on smoking status. Smokers liked the ads less and had fewer positive and more negative thoughts. Findings suggest a media campaign focusing on negative life circumstances can be an effective component of a tobacco control program aimed at adolescents. Mechanisms through which the negative life circumstances ads influence adolescents' intentions to smoke are discussed. Findings also suggest that smokers respond differently to anti-tobacco ads, and their responses need to be considered when developing effective anti-tobacco advertising campaigns. https://www.ncbi.nlm.nih.gov/pubmed/18661389
2008 Smoking status affects men and women differently on schizotypal traits and cognitive failures. Wan , L.,Friedman , B.H.,Boutros , N.N.,Crawford , H.J. Personality and Individual Differences 44 425-435
2006 P50 sensory gating: impact of high vs. low schizotypal personality and smoking status. Wan , L.,Crawford , H.J.,Boutros , N. International Journal of Psychophysiology 60 1-9
2012 Low-dose adolescent nicotine and methylphenidate have additive effects on adult behavior and neurochemistry. Wheeler , T. L.,Smith , L.N.,Bachus , S. E.,McDonald , C.G.,Fryxell , K.J.,Smith , R.F. Pharmacology Biochemistry and Behavior.
2005 Differences in food intake and exercise by smoking status in adolescents. Wilson , D.B.,Smith , B.N.,Speizer , I.S.,Bean , M.K.,Mitchell , K.S.,Uguy , L.S.,Fries , E.A. Preventive Medicine 40 872-879
2006a Association of the phosphatase and tension homolog gene (PTEN) with smoking initiation and nicotine dependence. Zhang , L.,Kendler , K.S.,Chen , X. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 141B 10-14
2006b The mu-opioid receptor gene and smoking initiation and nicotine dependence. Zhang , L.,Kendler , K.S.,Chen , X. Behavioral and Brain Functions 2 28
2018 Patterns and correlates of tobacco and cannabis co-use by tobacco product type: Findings from the Virginia Youth Survey Cobb , C. O.,Soule , E.K.,Rudy , A.K.,Sutter , M.,Cohn , A.M. . Substance Use and Misuse 53(14) 2310-2319 BACKGROUND: Cannabis use is more common among tobacco users than nonusers, and co-use (i.e., use of both substances individually) may be increasing. Better understanding of patterns and correlates of co-use is needed. The current study aimed to compare rates and correlates of tobacco and cannabis co-use by tobacco product among youth. METHODS: High school students who completed the 2013 Virginia Youth Survey and reported past 30-day tobacco use (cigarette, smokeless tobacco, cigar) were included (n = 1390). Prevalence of past 30-day tobacco-only and cannabis co-use was calculated. Demographic, tobacco, and other substance use characteristics were compared by co-use status. Multivariate logistic regression models examined correlates of co-use overall and by tobacco product. RESULTS: Over half of tobacco users were co-users. Poly-tobacco use, particularly combusted tobacco, was more prevalent among co-users. Past 30-day alcohol use and lifetime other illegal drug use/prescription drug misuse were common correlates of co-use. Black Non-Hispanic (NH) race/ethnicity was associated with co-use when restricted to cigarette users. "Other" race/ethnicity was associated with co-use in the overall model and when restricted to cigar users. Past 30-day cigarette smoking was associated with co-use in all models except among cigar smoking co-users. Conclusions/Importance: Rates and correlates of tobacco and cannabis co-use were not uniform and differed by tobacco product type. Tobacco and cannabis co-users may be at greater risk for negative health effects associated with inhaled tobacco and other risky substance use. The efficacy of prevention efforts may be improved if risk factors associated with product-specific co-use are considered. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/29963944
2018 Development and initial validation of a risk behavior diagnosis scale for e-cigarette use. In R. Umstattd Meyer (ed.), Proceedings of the American Academy of Health Behavior 2018 Annual Scientific Meeting: An Equity Approach to Health Behavior Innovations. Will , K.E.,Edwards , A.L.,Harrell , P.T.,Yilmaz , B.O.,Libby , E.P.,Mondejar , K.A.,Paulson , A.C.,Plunk , A.D.,Herman , M.C. Health Behavior Research 1 46
2018 Patterns and Profiles of Adolescent Tobacco Users: Results From the Virginia Youth Survey. Nicotine & tobacco research Sutter , M.E.,Everhart , R.S.,Miadich , S.,Rudy , A.K.,Nasim , A.,Cobb , C. Society for Research on Nicotine and Tobacco 20 S39-S47 Cigarette smoking has decreased to a record low among youth across the United States, including in Virginia. Rates of alternative tobacco use, however, are rising and polytobacco use is common. A better understanding of the shifting use patterns and associated risk factors is important for informing tobacco prevention, cessation, and policy efforts. Methods Weighted data from the 2013 Virginia Youth Survey were used. The sample was limited to 1168 youth who reported past 30-day tobacco use of ≥1 product (cigarettes, smokeless tobacco [smokeless], or cigars/little cigars/cigarillos [cigars]). Latent class analysis categorized individuals based on current tobacco use frequency/intensity. Multivariable multinomial logistic regressions compared classes on demographics, other tobacco-related factors, other substance use, and health/psychosocial factors. Results The five-class model indicated the best fit with classes characterized as "Chippers" (28.0%; high probability of low-frequency/intensity cigarette use), "Moderate Poly-Users" (23.6%; low- to high-frequency/moderate intensity cigarette use; moderate probability smokeless/cigar use), "Cigar Users" (20.9%; no-low-probability cigarette/smokeless use; high-probability cigar use), "Smokeless Users" (17.3%; no-low-probability cigarette/cigar use; moderate-high-probability smokeless use), and "Heavy Poly-Users" (10.4%; daily/high-intensity cigarette use, moderate-high-probability smokeless/cigar use). Classes differed significantly by demographics and inconsistently by other tobacco-related factors. Heavy Poly-Users were more likely to engage in other substance use behaviors, report suicidal ideation, and report being bullied because of gender. Conclusions Classes identified indicate that a large proportion of youth engage in polytobacco use and certain subgroups may be at greater risk for negative health consequences due to elevated psychosocial and behavioral risk factors. Implications These findings suggest distinct patterns of current tobacco use, including a high proportion of youth engaging in polytobacco use. Heavy polytobacco use co-occurs with other health risk behaviors and may be attributed to psychosocial risk factors. Results underscore the need for detailed monitoring of shifting youth tobacco use patterns as well as targeted prevention, cessation, and policy efforts. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093380/
2016 Text Message Delivered Peer Network Counseling for Adolescent Smokers: A Randomized Controlled Trial. Mason , M.,Mennis , J. ,Way , T.,Zaharakis , N.,Campbell , L.F.,Benotsch , E.G.,King , L. The Journey of Primary Prevention 37 403-420 Although adolescent tobacco use has declined in the last 10 years, African American high school seniors' past 30-day use has increased by 12 %, and as they age they are more likely to report lifetime use of tobacco. Very few urban youth are enrolled in evidenced-based smoking prevention and cessation programming. Therefore, we tested a text messaging smoking cessation intervention designed to engage urban youth through an automated texting program utilizing motivational interviewing-based peer network counseling. We recruited 200 adolescents (90.5 % African American) into a randomized controlled trial that delivered either the experimental intervention of 30 personalized motivational interviewing-based peer network counseling messages, or the attention control intervention, consisting of text messages covering general (non-smoking related) health habits. All adolescents were provided smart phones for the study and were assessed at baseline, and at 1, 3, and 6 months post intervention. Utilizing repeated measures general linear models we examined the effects of the intervention while controlling for race, gender, age, presence of a smoker in the home, and mental health counseling. At 6 months, participants in the experimental condition significantly decreased the number of days they smoked cigarettes and the number of cigarettes they smoked per day; they significantly increased their intentions not to smoke in the future; and significantly increased peer social support among girls. For boys, participants in the experimental condition significantly reduced the number of close friends in their networks who smoke daily compared to those in the control condition. Effect sizes ranged from small to large. These results provide encouraging evidence of the efficacy of text messaging interventions to reduce smoking among adolescents and our intervention holds promise as a large-scale public health preventive intervention platform. Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/27388626
2017 Exercise or saccharin during abstinence block estrus-induced increases in nicotine-seeking. Lynch , W.J.,Tan , L.,Narmeen , S,Beiter , R.,Brunzell , D.H. Recent evidence suggests that adolescent and young adult females may be particularly responsive to nicotine use interventions that include exercise or environmental enrichment. This possibility was addressed in the current study by comparing the efficacy of exercise versus non-exercise environmental enrichment (saccharin) during abstinence at reducing subsequent nicotine-seeking/relapse vulnerability in an adolescent-onset rat model. The efficacy of each intervention was examined as a function of estrous cycle phase given findings indicating that hormonal status influences relapse vulnerability and treatment outcome in females. Once adolescent female rats acquired nicotine self-administration, they were given 23-h/day access to nicotine (0.01mg/kg/infusion) for 10days. Following the last self-administration session, rats began a 10-day forced abstinence period with 2-h/day access to an unlocked wheel (exercise, n=15), a bottle containing a saccharin-sweetened solution (0.25%; saccharin, n=19), or without access to a wheel or saccharin (control, n=20). Nicotine-seeking, as assessed under an extinction/cued-induced reinstatement procedure, was examined on day 11 of abstinence. Levels of nicotine-seeking were highest in females tested during estrus as compared to females tested during non-estrus phases. Exercise or saccharin during abstinence reduced nicotine-seeking in females tested during estrus, but neither affected the low levels of nicotine-seeking observed in females tested during non-estrus phases, presumably due to a floor effect. These results demonstrate that exercise or saccharin during abstinence decrease nicotine-seeking, and suggest that either would be effective as an early intervention for nicotine use and addiction in females. University of Virginia https://www.ncbi.nlm.nih.gov/pubmed/29080668
2017 Behavioral Healthcare Staff Attitudes and Practices Regarding Consumer Tobacco Cessation Services Koch , J.R.,Breland , A. Journal of Behavioral Health Services & Research 44(3) Given the high prevalence of tobacco use among persons with behavioral health disorders, there has been much discussion about if and when tobacco cessation services should be provided to consumers. Approximately 1700 staff (who served adults and youth) from 38 public behavioral healthcare agencies in Virginia completed a survey on their attitudes and practices regarding tobacco cessation services for consumers. Results showed that most staff (88%) think tobacco cessation services should be offered and do not interfere with treatment. Most staff (57%) always/usually screened consumers for tobacco use, but few (14%) always/usually provided tobacco cessation counseling. Reported barriers included consumers not wanting to quit and a lack of staff training. Most staff reported that their organizations do not have policies regarding tobacco cessation services. Use of tobacco cessation practices was related to staff confidence using the practices, preparedness, and years of experience. Steps to improving the use of tobacco cessation practices in this setting are discussed. 399-413 Virginia Commonwealth University https://www.ncbi.nlm.nih.gov/pubmed/?term=Behavioral+Healthcare+Staff+Attitudes+and+Practices+Regarding+Consumer+Tobacco+Cessation+Services
2019 "Think it. Mix it. Vape it.": A content analysis on e-cigarette radio advertisements Nicksic , N. E.,Brosnan , P, G.,Chowdhury , N.,Barnes , A. J.,Cobb , C. O. Substance Use & Misuse Background: E-cigarette (EC) use is increasing rapidly across the United States, especially among youth. EC advertisements are one likely contributor to this increase, as they currently have few marketing restrictions. Radio advertising reaches most of the U.S. population and may be particularly influential in this regard. Objectives: The purpose of the current study was to examine content themes and spending data from EC radio advertisements. Methods: Competitrack, a marketing tracking firm, gathered 19 advertisements from four different EC brands across the United States from 2015 to 2016, which were coded by two individuals and analyzed for main content themes. Additionally, spending data were analyzed by identified EC brand. Results: Logic was the most common EC brand advertised on the radio and included themes potentially appealing to youth, such as humor and sound effects. Of the 28 analyzed content themes, references to "taste" were the most popular, followed by highlighting benefits of using ECs, presence of music, and comparison to other EC brands. Only Logic advertisements (n = 7) included health disclaimers and age restriction messages, yet frequently included themes that were attractive to youth. Conclusions/Importance: As these radio advertisements are exposing youth and other vulnerable populations to ECs, regulations, similar to those made for conventional cigarette advertising, are necessary for prevention efforts. Virginia Commonwealth University 10.1080/10826084.2019.1581219
2019 Is susceptibility to E-cigarettes among youth associated with tobacco and other substance use behaviors one year later? Results from the PATH study Nicksic , N. E,Barnes , A. J. Preventive Medicine 121 109-114 E-cigarettes are the most commonly used tobacco product among youth. In addition to harm potential, e-cigarette use is associated with initiating cigarette smoking. Limited research exists whether susceptibility to e-cigarette use is a risk factor for future tobacco and other substance use initiation. This study examined associations between baseline e-cigarette susceptibility and initiation and past 30-day use of e-cigarettes and cigarettes as well as initiation of marijuana and alcohol one year later, after adjusting for other risk factors and sociodemographic confounders. The study sample consisted of 5156 nationally representative youth (12-17 years) who completed both waves 1 (2013-2014) and 2 (2014-2015) of the Population Assessment of Tobacco and Health (PATH) study and were never users of tobacco, marijuana, and alcohol in Wave 1. Youth who were susceptible to e-cigarettes had increased odds of initiating e-cigarettes (adjusted OR: 2.22, 95% CI: 1.55-3.18), marijuana (aOR: 1.66, 95% CI: 1.12-2.46), and alcohol (aOR: 1.61, 95% CI: 1.26-2.06) between waves, as well as past reporting 30-day e-cigarette use (aOR: 3.64, 95% CI: 1.93-6.89) in Wave 2. Additionally, cigarette susceptibility, but not e-cigarette susceptibility, was associated with cigarette initiation (aOR: 3.36, 95% CI: 1.95-5.82) and past 30-day use (aOR: 2.83, 95% CI: 1.34-5.97). Prevention policies, as well as future research, could target youth susceptible to e-cigarettes to reduce the current trends on the use of these alternative tobacco products. Such efforts may also reduce the use of cigarettes and other substances. Virginia Commonwealth University 10.1016/j.ypmed.2019.02.006
2019 Reasons to use e-cigarettes among adults and youth in the Population Assessment of Tobacco and Health (PATH) study Nicksic , N. E.,Snell , L. M. ,Barnes , A. J. Addictive Behaviors 93 93-99 BACKGROUND: While e-cigarette use is increasing, reasons to use e-cigarettes are poorly summarized in the literature. The objective of this study was to organize reasons to use e-cigarette items into factors and determine associations between these factors and e-cigarette user characteristics. METHODS: Data were drawn from youth (12-17) and adults (18+) in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) study. Exploratory factor analysis was conducted on 13 reasons to use survey items from experimental and established adult e-cigarette users and past 30 day youth e-cigarette users to determine two factors - "alternative to cigarettes" and "larger social environment". Weighted linear regression models tested the associations between e-cigarette user group and sociodemographics and reasons to use factors among youth and adults. RESULTS: Adult current established e-cigarette users were associated with both alternative to cigarettes (β = 0.128, p < .001) and larger social environment (β = 0.063, p < .001) factors, while former established e-cigarette users were associated with alternative to cigarettes (β = 0.064, p < .001). Several adult sociodemographic characteristics were associated with one but not the other factor, or both but in opposite directions. Youth that used e-cigarettes earlier today were also associated with both reasons to use factors (β = 0.127-0.130, p < .01, each); however, youth using any other day in the past 30 days was not associated with either factor. CONCLUSIONS: Reasons to use are associated with patterns of e-cigarette use among youth and adults. These factors could support a comprehensive approach to addressing rising e-cigarette use among youth and adults and target certain user populations. Virginia Commonwealth University 10.1016/j.addbeh.2019.01.037
2018 Patterns and profiles of adolescent tobacco users: Results from the Virginia Youth Survey Sutter , M. E.,Everhart , R. S.,Miadich , S.,Rudy , A. K.,Nasim , A.,Cobb , C. O. Nicotine & Tobacco Research 20 S39-S47 Background: Cigarette smoking has decreased to a record low among youth across the United States, including in Virginia. Rates of alternative tobacco use, however, are rising and polytobacco use is common. A better understanding of the shifting use patterns and associated risk factors is important for informing tobacco prevention, cessation, and policy efforts. Methods: Weighted data from the 2013 Virginia Youth Survey were used. The sample was limited to 1168 youth who reported past 30-day tobacco use of ≥1 product (cigarettes, smokeless tobacco [smokeless], or cigars/little cigars/cigarillos [cigars]). Latent class analysis categorized individuals based on current tobacco use frequency/intensity. Multivariable multinomial logistic regressions compared classes on demographics, other tobacco-related factors, other substance use, and health/psychosocial factors. Results: The five-class model indicated the best fit with classes characterized as "Chippers" (28.0%; high probability of low-frequency/intensity cigarette use), "Moderate Poly-Users" (23.6%; lowto high-frequency/moderate intensity cigarette use; moderate probability smokeless/cigar use), "Cigar Users" (20.9%; no-low-probability cigarette/smokeless use; high-probability cigar use), "Smokeless Users" (17.3%; no-low-probability cigarette/cigar use; moderate-high-probability smokeless use), and "Heavy Poly-Users" (10.4%; daily/high-intensity cigarette use, moderate- high-probability smokeless/cigar use). Classes differed significantly by demographics and inconsistently by other tobacco-related factors. Heavy Poly-Users were more likely to engage in other substance use behaviors, report suicidal ideation, and report being bullied because of gender. Conclusions: Classes identified indicate that a large proportion of youth engage in polytobacco use and certain subgroups may be at greater risk for negative health consequences due to elevated psychosocial and behavioral risk factors. Implications: These findings suggest distinct patterns of current tobacco use, including a high proportion of youth engaging in polytobacco use. Heavy polytobacco use co-occurs with other health risk behaviors and may be attributed to psychosocial risk factors. Results underscore the need for detailed monitoring of shifting youth tobacco use patterns as well as targeted prevention, cessation, and policy efforts. Virginia Commonwealth University https://doi.org/10.1093/ntr/nty032
2019 Cigarette and e-cigarette use and social perceptions over the transition to college: The role of ADHD symptoms Dvorsky , M. R.,Langberg , J. M. Psychology of Addictive Behaviors 33 318-330 Cigarette and electronic cigarette (e-cigarette) use prevalence increases during adolescence and peaks in young adulthood, with substantial increases during the transition from high school to college especially more recently for e-cigarette use. It is important to identify the underlying factors that serve as risk factors for tobacco use and social perceptions about cigarette and e-cigarette use. It is unknown whether attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with social perceptions about tobacco or increased tobacco use during the high school to college transition. This three timepoint prospective longitudinal study evaluates the reciprocal relationship between ADHD symptoms and social perceptions about tobacco as well as the frequency of cigarette and e-cigarette use in a sample of 150 high school seniors (Mage = 18.25, 66.0% female, 65.3% White) across the transition to college. ADHD symptoms in high school predicted increases in e-cigarette use during the first semester of college, and this association maintained through the end of the first year. ADHD symptoms predicted changes in social perceptions about cigarette and e-cigarette use after the transition to college. ADHD symptoms were predicted by social perceptions about e-cigarettes at the beginning of college. Understanding the psychosocial mechanisms underlying the pathways from ADHD symptoms to e-cigarette use may advance tobacco use etiology and prevention efforts, which is important considering the rapid growth in e-cigarette use among emerging adults. Virginia Commonwealth University http://dx.doi.org/10.1037/adb0000450
2019 Exercise during abstinence normalizes ultrastructural synaptic plasticity associated with nicotine-seeking following extended access self-administration Sanchez , V.,Bakhti-Suroosh , A.,Chen , A.,Brunzell , D. H.,Erisir , A.,Lynch , W. J. European Journal of Neuroscience Nicotine‐craving progressively increases, or incubates, over abstinence following extended access self‐administration. While not yet examined for nicotine, the incubation of cocaine‐seeking is accompanied by changes in synaptic plasticity in the nucleus accumbens. Here, we determined whether such changes also accompany enhanced nicotine‐seeking following extended access self‐administration and abstinence, and whether exercise, a potential intervention for nicotine addiction, may exert its efficacy by normalizing these changes. Given that in humans, tobacco/nicotine use begins during adolescence, we used an adolescent‐onset model. Nicotine‐seeking was assessed in male rats following extended access nicotine or saline self‐administration (23‐hr/day, 10 days) and 10 days of abstinence, conditions known to induce the incubation of nicotine‐seeking, using a within‐session extinction/cue‐induced reinstatement procedure. A subset of rats had 2‐hr/day access to a running wheel during abstinence. Ultrastructural alterations of synapses in the nucleus accumbens core and shell were examined using electron microscopy. Nicotine‐seeking was elevated following extended access self‐administration and abstinence (in sedentary group), and levels of seeking were associated with an increase in the density of asymmetric (excitatory) and symmetric (inhibitory) synapses onto dendrites in the core, as well as longer asymmetric synapses onto spines, a marker of synaptic potentiation, in both the core and shell. Exercise normalized each of these changes; however, in the shell, exercise and nicotine similarly increased the synapse length. Together, these findings indicate an association between nicotine‐seeking and synaptic plasticity in the nucleus accumbens, particularly the core, and indicate that the efficacy of exercise to reduce nicotine‐seeking may be mediated by reversing these adaptations. University of Virginia 10.1111/ejn.14408
2019 Exercise or saccharin during abstinence block estrus-induced increases in nicotine-seeking Lynch , W. J.,Tan , L.,Narmeen , S.,Beiter , R.,Brunzell , D. H. Physiology and Behavior 201 33-41 Recent evidence suggests that adolescent and young adult females may be particularly responsive to nicotine use interventions that include exercise or environmental enrichment. This possibility was addressed in the current study by comparing the efficacy of exercise versus non-exercise environmental enrichment (saccharin) during abstinence at reducing subsequent nicotine-seeking/relapse vulnerability in an adolescent-onset rat model. The efficacy of each intervention was examined as a function of estrous cycle phase given findings indicating that hormonal status influences relapse vulnerability and treatment outcome in females. Once adolescent female rats acquired nicotine self-administration, they were given 23-h/day access to nicotine (0.01mg/kg/infusion) for 10days. Following the last self-administration session, rats began a 10-day forced abstinence period with 2-h/day access to an unlocked wheel (exercise, n=15), a bottle containing a saccharin-sweetened solution (0.25%; saccharin, n=19), or without access to a wheel or saccharin (control, n=20). Nicotine-seeking, as assessed under an extinction/cued-induced reinstatement procedure, was examined on day 11 of abstinence. Levels of nicotine-seeking were highest in females tested during estrus as compared to females tested during non-estrus phases. Exercise or saccharin during abstinence reduced nicotine-seeking in females tested during estrus, but neither affected the low levels of nicotine-seeking observed in females tested during non-estrus phases, presumably due to a floor effect. These results demonstrate that exercise or saccharin during abstinence decrease nicotine-seeking, and suggest that either would be effective as an early intervention for nicotine use and addiction in females. University of Virginia 10.1016/j.physbeh.2017.10.026
In Press Comparison of two cohorts of medically at-risk adolescents engaging in substance use: Clinical predictors for monitoring care Hollen , P. J.,O'Laughlen , M. C.,Hellems , M. A.,Hinton , I.,Xin , W.,Patrie , J. T. Journal of the American Association of Nurse Practitioners University of Virginia
2019 Adverse childhood experiences and e‐cigarette sse during young adulthood Shin , S. H.,Conley , D.,Jiskrova , G. K.,Wills , T. A. The American Journal on Addictions Background and Objectives: E‐cigarette use among young peopleis highly prevalent. Individuals exposed to adverse childhood ex-periences such as childhood maltreatment (CM) may be at particularrisk, as CM has been linked to nicotine dependence. Studies testingthe association between CM and e‐cigarette use are lacking,including research that examines pathways linking CM toe‐cigarette use.Methods:Using a community sample of young adults (N=208;ages 18‐21), we examined the relationship between CM ande‐cigarette use and explored the potential role of impulsivity inlinking CM to e‐cigarette use via a series of structural equationmodels controlling for demographic characteristics.Results:CM was significantly associated with lifetime e‐cigaretteuse. Furthermore, CM was associated with negative urgency (NU),whereas NU and sensation seeking were significantly related tolifetime e‐cigarette use. NU fully mediated the relationship betweenCM and lifetime e‐cigarette use.Conclusions and Scientific Significance:Our results suggest thatyoung adults with a history of CM might be vulnerable to e‐cigaretteuse and that NU played a significant role in linking CM to lifetimee‐cigarette use. Addressing NU in young adults with a history ofCM might be a useful avenue for preventing e‐cigarette use in thispopulation. Virginia Commonwealth University 10.1111/ajad.12890
2016 Nicotine consumption is strongly influenced by social interactions in male, but not female, adolescent mice Hudson , A.D.,Murphy , R.L.,Fryxell , K.J. Society for Neuroscience Abstracts George Mason University
Adolescents' Response to a Text Message-Delivered Tobacco Use Intervention by Depressive Symptoms and Sex. Mason , M.,Coatsworth , J.D. Journal of Child and Adolescent Substance Abuse. Virginia Commonwealth University
2019 Impact of Menthol on Oral Nicotine Consumption in Female and Male Sprague Dawley Rats. Bagdas , D.,Cam , B.,Gul , Z.,Scott , M.M.,Tyndal , R.F.,Buyukuysal , R.L.,Damaj , M.I. Nicotine & Tobacco Research. 22 196-203 Introduction One of the preferable flavors in oral nicotine delivery systems is menthol which masks the harshness of tobacco. However, possible interactions between oral menthol and nicotine on intake and preference remain unclear. Therefore, we aimed to determine the impact of menthol on oral nicotine consumption. Methods Adult Sprague Dawley female and male rats (n = 8 per group) were given a choice of water or drug solution by using two-bottle free choice paradigm for 2 weeks: vehicle (5% ethanol), nicotine (20 mg/L), menthol (1 g/L) and mentholated nicotine groups. At the end of the study, plasma nicotine levels were determined. Results When rats were given a choice of nicotine or water, nicotine intake was similar between female and male rats. Menthol addition to nicotine solution significantly increased nicotine intake and preference in male but not female rats without a considerable effect on total fluid intake and body weight change in either sex. The average nicotine intake in male rats was 0.5 ± 0.05 and 1.4 ± 0.12 mg/kg/day for nicotine and menthol-nicotine combination (p < .05), respectively. The average nicotine intake in female rats was 0.6 ± 0.05 and 0.6 ± 0.03 mg/kg/day for nicotine and menthol-nicotine combination (p > .05), respectively. Plasma nicotine levels were not significantly different between the groups in either male (nicotine group: 20.8 ± 4.9, mentholated nicotine group: 31.9 ± 3.2 ng/mL) or female (nicotine group: 24.0 ± 3.3, mentholated nicotine group: 17.8 ± 2.9 ng/mL) rats (p > .05). Conclusions Menthol increases oral nicotine consumption in male, but not female, rats. Implications This study may provide data on the co-use of menthol and nicotine in smokeless tobacco, particularly oral dissolvable tobacco products. Virginia Commonwealth University doi.org/10.1093/ntr/ntz019
2017 Effect of flavors and modified risk messages on e-cigarette abuse liability. Barnes , A.J.,Bono , R.S.,Lester , R.C.,Eissenberg , T.E.,Cobb , C.O. Tobacco Regulatory Science 3(4) 374-387 Objectives: We measured e-cigarettes' abuse liability compared to conventional tobacco cigarettes under flavor and message conditions amenable to regulation. Methods: Two studies used 2 x 2 within-subjects designs with factors of e-cigarette flavor (Study 1: tobacco vs menthol; Study 2: cherry vs unflavored) and message (Study 1: reduced harm vs no message; Study 2: reduced exposure to carcinogens vs no message) with cigarette smokers (N(total) = 36). Linear mixed effects models assessed abuse liability for tobacco products. Outcomes included the price after which consumption is zero (the maximum amount participants would pay for a tobacco product) from the multiple-choice procedure (MCP) and cigarette purchase task (CPT) and demand elasticity (price sensitivity) from the CPT. Results: In the MCP, the price where consumption reached zero was significantly lower in all e-cigarette conditions except tobacco flavor (message or no message) compared to cigarettes (ps < .05). Demand elasticity was significantly higher for menthol/no message and unflavored/reduced exposure message conditions relative to cigarettes (ps < .05). Conclusions: Flavors and modified risk messages included with e-cigarettes may affect e-cigarette abuse liability among smokers, suggesting regulatory pathways to influence demand for conventional and alternative tobacco products. Virginia Commonwealth University
2019 Effects of electronic cigarette liquid flavors and modified risk messages on perceptions and subjective effects of e-cigarettes. Bono , R.S.,Barnes , A.J.,Lester , R.C.,Cobb , C.O. Health Education Behavior 46(2) 197-203 Understanding how two characteristics-flavors and modified risk messages-affect perceptions and subjective effects of electronic cigarettes (e-cigarettes) can inform tobacco control efforts. In two within-subjects studies (N = 17 and N = 19), the effects of e-cigarette flavors (tobacco vs. menthol and unflavored vs. cherry) and hypothetical modified risk messages ("reduced harm relative to cigarettes" vs. no message and "reduced carcinogen exposure relative to cigarettes" vs. no message) on cigarette smokers' perceptions of e-cigarettes were measured after participants self-administered condition-specific products (own-brand cigarettes; e-cigarettes). Perceptions/subjective effects were tested using linear mixed-effects regressions. Cigarettes were perceived as most harmful but rated more positively than e-cigarettes (ps < .05). Cherry and menthol e-cigarettes increased perceived pleasantness, taste, and physical sensations compared with unflavored and tobacco-flavored e-cigarettes, respectively (ps < .05). Modified risk messages were associated with reduced ratings of aversive effects (ps < .05) but not harm perceptions. Overall, few perceptions/subjective effects differed by e-cigarette flavor or message. Flavors and messages may have some influence on how smokers experience e-cigarettes. Virginia Commonwealth University doi: 10.1177/1090198118806965
2019 Rethink Vape: Development and evaluation of a risk communication campaign for e-cigarettes. In M. Reed (Ed.), "The American Academy of Health Behavior 2019 Annual Scientific Meeting: Theory and Applications of Multiple Health Behavior Change" England , K.,Edwards , A.L.,Paulson , A.C.,Harrell , P.T.,Libby , E.P. Health Behavior Research: Vol. 2: No. 2. 10 Eastern Virginia Medical School
2018 Addressing barriers to recruitment, retention, and implementation of parenting programs: Lessons learned for effective program delivery in rural and urban areas. Smokowski , P,Corona , R,Bacallao , M,Marshall , M,Fortson , B,Yaros , A Journal of Child and Family Studies 27 2925-2942
2017 Adolescent Perceptions and Experience Regarding Electronic Nicotine Delivery Systems(ENDS): Recommendations for Intervention Development. Proceedings on the 17th Annual Meeting of the American Academy of Health Behavior Will , K.E,Paulson , K.A ,Herman , A.C Health Behavior Research 1(1) 11
2014 Anxiety status affects nicotine- and baclofen-induced locomotor activity, anxiety, and single trial conditioned place preference in male adolescent rats. Gholap , V.,Halquist , M.S.,Smith , R.F. Developmental Psychobiology 56(6) 1352-1364 Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety‐like behavior on single‐trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety‐like behavior in rats divided into high‐anxiety and low‐anxiety groups. Baclofen decreased locomotor behavior in high‐anxiety rats. Baclofen alone failed to produce differences in anxiety‐like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High‐ and low‐anxiety groups also showed differences in single‐trial nicotine‐induced place preference. Only high‐anxiety rats formed place preference to nicotine, while rats in the low‐anxiety group formed no conditioned place preference. These results suggest that among adolescents, high‐anxiety individuals are more likely to show preference for nicotine than low‐anxiety individuals. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1352-1364, 2014. Virginia Commonwealth University
2020 'An Analytical Perspective on Determination of Free Base Nicotine in e-Liquids' Gholap , V. V.,Heyder , R. S.,Kosmider , L.,Halquist , M.S. Journal of Analytical Methods in Chemistry 3 In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to >50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated ("free base") forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson-Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson-Hasselbalch method was tested using potentiometric titration. The accuracy was found to be >98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids. Virginia Commonwealth University
2019 Effect of menthol on nicotine intake and relapse vulnerability in rat model of concurrent intravenous menthol/nicotine self-administration. Nesil , T,Narmeen , S,Bakhti-Suroosh , A,Lynch , W.J Psychopharmacology
2017 Does exposure and receptivity to e-cigarette advertisements relate to e-cigarette and conventional cigarette use behaviors among youth? Results from wave 1 of the Population Assessment of Tobacco and Health Study Nicksic , N.E,Snell , L.M,Barnes , A.J Journal of Applied Research on Children: Informing Policy for Children at Risk 8(2) 1-18
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