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Sample records for adolescent nicotine dependence

  1. Nicotine Dependence and Problem Behaviors Among Urban South African Adolescents

    PubMed Central

    Pahl, Kerstin; Brook, David W.; Morojele, Neo K.; Brook, Judith S.

    2010-01-01

    Tobacco use and its concomitant, nicotine dependence, are increasing in African countries and other parts of the developing world. However, little research has assessed nicotine dependence in South Africa or other parts of the African continent. Previous research has found that adolescent problem behaviors, including tobacco use, tend to cluster. This study examined the relationship between nicotine dependence and adolescent problem behaviors in an ethnically diverse sample of urban South African adolescents. A community sample (N = 731) consisting of “Black,” “White,” “Coloured,” and “Indian” youths aged 12–17 years was drawn from the Johannesburg metropolitan area. Structured interviews were administered by trained interviewers. Nicotine dependence was assessed by the Fagerström Test of Nicotine Dependence. Logistic regression analyses showed that higher levels of nicotine dependence significantly predicted elevated levels of violent behavior, deviant behavior, marijuana and other illegal drug use, binge drinking, early sexual intercourse, multiple sexual partners, and inconsistent condom use, despite control on the adolescents’ demographic characteristics, peer smoking, conflict with parents, peer deviance, and the availability of legal and illegal substances. These relationships were robust across ethnicity and gender. The findings indicate the need for policy makers and prevention and intervention programs in South Africa to consider adolescent nicotine dependence in conjunction with comorbid problem behaviors, including other substance use, sexual risk behaviors, and deviant behaviors. PMID:20099015

  2. Risk and Protective Factors for Nicotine Dependence in Adolescence

    ERIC Educational Resources Information Center

    Hu, Mei-Chen; Griesler, Pamela; Schaffran, Christine; Kandel, Denise

    2011-01-01

    Background: We investigated the role of psychosocial and proximal contextual factors on nicotine dependence in adolescence. Methods: Data on a multiethnic cohort of 6th to 10th graders from the Chicago public schools were obtained from four household interviews conducted with adolescents over two years and one interview with mothers. Structural…

  3. Risk and Protective Factors for Nicotine Dependence in Adolescence

    PubMed Central

    Hu, Mei-Chen; Griesler, Pamela; Schaffran, Christine; Kandel, Denise

    2010-01-01

    Background We investigated the role of psychosocial and proximal contextual factors on nicotine dependence in adolescence. Methods Data on a multiethnic cohort of 6th to 10th graders from the Chicago public schools were obtained from four household interviews conducted with adolescents over two years and one interview with mothers. Structural equation models were estimated on 660 youths who had smoked cigarettes by the first interview. Results Pleasant initial sensitivity to tobacco use, parental nicotine dependence (ND), adolescent ND and extensiveness of smoking at the initial interview had the strongest total effects on adolescent ND two years later. Perceived peer smoking and adolescent conduct problems were of lesser importance. Parental ND directly impacted adolescent ND two years later and had indirect effects through pleasant initial sensitivity and initial extensiveness of smoking. Parental depression affected initial adolescent dependence and depression but adolescent depression had no effect on ND. The model had greater explanatory power for males than females due partly to the stronger effect of conduct problems on dependence for males than females. Conclusions The findings underscore the importance of the initial drug experience and familial factors on adolescent nicotine dependence and highlight the factors to be the focus of efforts targeted toward preventing ND among adolescents. PMID:21250992

  4. Intergenerational Patterns of Smoking and Nicotine Dependence Among US Adolescents

    PubMed Central

    Griesler, Pamela C.; Hu, Mei-Chen

    2015-01-01

    Objectives. We examined associations between parental and adolescent smoking and nicotine dependence in the United States. Methods. We used data from the 2004 to 2012 National Survey on Drug Use and Health, which ascertained smoking behaviors of 1 parent and 1 adolescent aged 12 to 17 years in 35 000 dyads. We estimated associations between parental and adolescent smoking behaviors, adjusted for covariates. Results. Parental current dependence was strongly associated with adolescents’ lifetime smoking (adjusted odds ratio [AOR] = 2.96; 95% confidence interval [CI] = 2.47, 3.55), whereas parental current nondependent smoking (AOR = 2.26; 95% CI = 1.92, 2.67) and former smoking (AOR = 1.51; 95% CI = 1.31, 1.75) were less strongly associated. Only parental nicotine dependence was associated with adolescent nicotine dependence (AOR = 1.66; 95% CI = 1.00, 2.74). Associations between parental and adolescent smoking did not differ by race/ethnicity. Parents’ education, marital status, and parenting and adolescents' mental health, beliefs about smoking, perception of schoolmates’ smoking, and other substance use predicted adolescent smoking and dependence. Conclusions. Reducing parental smoking would reduce adolescent smoking. Prevention efforts should encourage parental smoking cessation, improve parenting, address adolescent mental health, and reinforce adolescents' negative beliefs about smoking. PMID:26378847

  5. Nicotine Dependence and Alcohol Problems from Adolescence to Young Adulthood

    PubMed Central

    Dierker, Lisa; Selya, Arielle; Rose, Jennifer; Hedeker, Donald; Mermelstein, Robin

    2016-01-01

    Background Despite the highly replicated relationship between symptoms associated with both alcohol and nicotine, little is known about this association across time and exposure to both drinking and smoking. In the present study, we evaluate if problems associated with alcohol use are related to emerging nicotine dependence symptoms and whether this relationship varies from adolescence to young adulthood, after accounting for both alcohol and nicotine exposure. Methods The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which measured smoking, nicotine dependence, alcohol use and alcohol related problems over 6 assessment waves spanning 6 years. Analyses were based on repeated assessment of 864 participants reporting some smoking and drinking 30 days prior to individual assessment waves. Mixed-effects regression models were estimated to examine potential time, smoking and/or alcohol varying effects in the association between alcohol problems and nicotine dependence. Findings Inter-individual differences in mean levels of alcohol problems and within subject changes in alcohol problems from adolescence to young adulthood were each significantly associated with nicotine dependence symptoms over and above levels of smoking and drinking behaviour. This association was consistent across both time and increasing levels of smoking and drinking. Conclusions Alcohol related problems are a consistent risk factor for nicotine dependence over and above measures of drinking and smoking and this association can be demonstrated from the earliest experiences with smoking in adolescents, through the establishment of more regular smoking patterns across the transition to young adulthood. These findings add to accumulating evidence suggesting that smoking and drinking may be related through a mechanism that cannot be wholly accounted for by exposure to either substance. PMID:27610424

  6. DEVELOPMENTAL TRAJECTORIES OF CRITERIA OF NICOTINE DEPENDENCE IN ADOLESCENCE*

    PubMed Central

    Hu, Mei-Chen; Muthén, Bengt; Shaffran, Christine C.; Griesler, Pamela; Kandel, Denise B.

    2008-01-01

    We describe the nature and predictors of developmental trajectories of symptoms of DSM-IV nicotine dependence in adolescence following smoking initiation. Data are from a longitudinal cohort of 324 new smokers from grades 6 to 10 in the Chicago Public Schools, interviewed 5 times at 6 month intervals. Monthly data on DSM-IV symptoms of nicotine dependence were available for 36 months. Growth mixture modeling was applied to the monthly histories to identify trajectories of DSM-IV criteria of nicotine dependence. A four-class solution best fitted the data: No DSM criterion (47.7%); Early onset/Chronic course (19.8%); Early onset/Remission (17.3%); Late onset (15.2%). Blunt use prior to cigarette use was associated with the three symptomatic trajectories. Conduct disorder and prior heavy smoking were associated with Class 2 (Chronic). Conduct disorder differentiated Class 2 from Class 4 (Late onset), while pleasant initial sensitivity to the first tobacco experience was associated with Classes 2 and 3 (Remit) and differentiated Class 2 from Class 4. Novelty seeking characterized Class 3. Parental dependence differentiated chronicity (Class 2) from remission (Class 3) among those who developed symptoms early. Being Hispanic reduced membership in Classes 3 and 4, and being male for Class 3. The data highlight the importance of parental nicotine dependence as a risk factor for early and sustained nicotine dependence by the offspring, pleasant initial sensitivity and conduct disorder for early onset of dependence, and blunt use prior to smoking for all trajectories. The factors important for onset of dependence are not necessarily the same as those for sustained course. PMID:18602225

  7. Comorbidity of Psychiatric Disorders and Nicotine Dependence among Adolescents: Findings from a Prospective, Longitudinal Study

    ERIC Educational Resources Information Center

    Griesler, Pamela C.; Hu, Mei-Chen; Schaffram, Christine; Kandel, Denise B.

    2008-01-01

    The relationship between nicotine dependence and DSM-IV psychiatric disorders in 1,039 adolescents is examined. Findings revealed that psychiatric disorders most usually predicted the onset of the first basis of nicotine dependence while nicotine dependence does not appear to have an influence on the onset of psychiatric disorders. Other…

  8. Bupropion SR in Adolescents with Comorbid ADHD and Nicotine Dependence: A Pilot Study

    ERIC Educational Resources Information Center

    Upadhyaya, Himanshu P.; Brady, Kathleen T.; Wang, Wei

    2004-01-01

    Objective: Bupropion SR has been shown to be effective for the treatment of nicotine dependence in adults. This open-label pilot study was designed to examine the feasibility and preliminary tolerability of bupropion SR in adolescents with nicotine dependence. Method: Sixteen adolescents aged 12 to 19 years were enrolled in the study. Eleven of…

  9. Evaluation of the level of nicotine dependence among adolescent smokers.

    PubMed

    Hrubá, D; Zachovalová, L; Fiala, J; Kyasová, M

    2003-09-01

    42.6% of urinary cotinine level variability (converted to the density measured by creatinine content) and 65.8% of variability of CO content in the air exhaled. It was demonstrated that regular adolescent smokers at the ages between 15 to 17 years inhaled the cigarette smoke and the young smokers' inner exposure to nicotine had been proved as well. In this age group, there are many individuals who have a strong or a very strong dependence on nicotine. As a result, it is necessary to promote smoking cessation and nicotine dependence treatment by recommending pharmaceuticals of substantial nicotine therapy. PMID:14514171

  10. [Nicotine dependence].

    PubMed

    Kawazoe, Shingo; Shinkai, Takahiro

    2015-09-01

    Smoking is the most widespread addictive behavior in the world, and it causes physical and psychological dependence on nicotine. As for physical nicotine dependence, nicotine produces rewarding effects by interacting with nicotinic acetylcholine receptors on neurons in the brain's reward system. Psychological dependence on nicotine comes with a complex psychological procedure that is based on distorted cognition which justifies their smoking behavior. Clinicians should support smokers with willingness to quit smoking comprehensively with this knowledge, although the success rate of smoking cessation is no ideal in general. PMID:26394514

  11. The relationship between impulsivity, risk-taking propensity and nicotine dependence among older adolescent smokers.

    PubMed

    Ryan, Katherine K; Mackillop, James; Carpenter, Matthew J

    2013-01-01

    Impulsivity and risk-taking propensity are neurobehavioral traits that reliably distinguish between smoking and non-smoking adults. However, how these traits relate to smoking quantity and nicotine dependence among older adolescent smokers is unclear. The current study examined impulsivity and risk-taking propensity in relation to smoking behavior and nicotine dependence among current older adolescent smokers (age 16-20 years; N=107). Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), the Balloon Analogue Risk Task (BART), and self-report measures of smoking behavior and nicotine dependence. Results indicated a significant positive relationship between nicotine dependence and the Attention subscale (β=.20, t=2.07, p<.05) and the Non-planning subscale (β=.19, t=1.92, p<.06) of the BIS-11. Contrary to expectation, the results also indicated a significant negative relationship between performance on the BART and nicotine dependence (β=-.19, t=-2.18, p<.05), such that greater risk-taking propensity was associated with less dependence. These data suggest that impulsivity and risk-taking propensity are related to older adolescent smoking but are separable traits with distinguishable associations with nicotine dependence among adolescents. These findings support the notion that impulsivity is related to heightened nicotine dependence, but suggest that the relationship between risk-taking propensity and nicotine dependence is more ambiguous and warrants further investigation. PMID:23006247

  12. Comorbidity of Psychiatric Disorders and Nicotine Dependence Among Adolescents: Findings From a Prospective, Longitudinal Study

    PubMed Central

    Griesler, Pamela C.; Hu, Mei-Chen; Schaffran, Christine; Kandel, Denise B.

    2008-01-01

    Objective To examine prospectively the comorbidity of DSM-IV psychiatric disorders and nicotine dependence in adolescence. Method A multiethnic sample (N = 1,039) of adolescents from grades 6 to 10 in the Chicago public schools (mean age 14.1 years) was interviewed at home five times, and mothers were interviewed three times over a 2-year period (2003–2005). Completion rates at each wave were 96% of the initial sample. Selected DSM-IV psychiatric disorders were ascertained from youths and mothers about youths at two annual waves with the NIMH Diagnostic Interview Schedule for Children, Version IV-Y and IV-P; DSM-IV symptoms of nicotine dependence were ascertained from youths at every wave using a measure developed for adolescents. Results Psychiatric disorders most often preceded the onset of the first criterion of nicotine dependence. Prospective associations between psychiatric disorders and nicotine dependence were examined through logistic regressions. After controlling for comorbid disorders, it was found that lifetime disruptive disorder significantly predicted the onset of a nicotine dependence criterion (adjusted odds ratio 2.1). Early onset of any psychiatric disorder increased this risk. Other predictors included novelty seeking and extensiveness of smoking. By contrast, nicotine dependence did not predict the onset of a psychiatric disorder; significant predictors included the youths' prior other psychiatric disorders, novelty seeking, and parental depression and antisocial behavior. Conclusions Nicotine dependence does not seem to contribute to the onset of psychiatric disorders, whereas disruptive disorder is an important etiologic factor for nicotine dependence in adolescence. PMID:18827718

  13. Time-varying effects of smoking quantity and nicotine dependence on adolescent smoking regularity

    PubMed Central

    Selya, Arielle S.; Dierker, Lisa C.; Rose, Jennifer S.; Hedeker, Donald; Tan, Xianming; Li, Runze; Mermelstein, Robin J.

    2012-01-01

    Background Little is known about time-varying effects of smoking quantity and nicotine dependence on the regularity of adolescent smoking behavior. Methods The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which followed adolescent smokers over 5 assessment waves spanning 48 months. Participants included former experimenters (smoked <100 cigarettes/lifetime but did not smoke in past 90 days), recent experimenters (smoked <100 cigarettes/lifetime and smoked in past 90 days), and current smokers (smoked >100 cigarettes/lifetime and smoked in past 30 days). Mixed-effects regression models were run to examine the time-varying effects of smoking quantity and nicotine dependence on regularity of smoking behavior, as measured by number of days smoked. Results Smoking quantity and nicotine dependence were each found to be significantly associated with regularity of adolescent smoking and the size of each effect exhibited significant variation over time. The effect of smoking quantity decreased across time for each smoking group, while the effect of nicotine dependence increased across time for former and recent experimenters. By the 48-month follow-up, the effects of smoking quantity and nicotine dependence had each stabilized across groups. Conclusions This study reveals that smoking quantity and nicotine dependence are not static risk factors for the development of more regular smoking patterns. At low levels of smoking when nicotine dependence symptoms are less common, smoking quantity is a stronger predictor of increased regularity of smoking, while for more experienced smokers, nicotine dependence predicts further increases in regularity. PMID:22995764

  14. Early-Emerging Nicotine Dependence Has Lasting and Time-Varying Effects on Adolescent Smoking Behavior.

    PubMed

    Selya, Arielle S; Dierker, Lisa; Rose, Jennifer S; Hedeker, Donald; Mermelstein, Robin J

    2016-08-01

    Novice and light adolescent smokers can develop symptoms of nicotine dependence, which predicts smoking behavior several years into the future. However, little is known about how the association between these early - emerging symptoms and later smoker behaviors may change across time from early adolescence into young adulthood. Data were drawn from a 7-year longitudinal study of experimental (<100 cigarettes/lifetime; N = 594) and light (100+ cigarettes/lifetime, but ≤5 cigarettes/day; N = 152) adolescent smokers. Time-varying effect models were used to examine the relationship between baseline nicotine dependence (assessed at age 15 ± 2 years) and future smoking frequency through age 24, after controlling for concurrent smoking heaviness. Baseline smoking status, race, and sex were examined as potential moderators of this relationship. Nicotine dependence symptoms assessed at approximately age 15 significantly predicted smoking frequency through age 24, over and above concurrent smoking heaviness, though it showed declining trends at older ages. Predictive validity was weaker among experimenters at young ages (<16), but stronger at older ages (20-23), relative to light smokers. Additionally, nicotine dependence was a stronger predictor of smoking frequency for white smokers around baseline (ages 14.5-16), relative to nonwhite smokers. Nicotine dependence assessed in mid-adolescence predicts smoking frequency well into early adulthood, over and above concurrent smoking heaviness, especially among novice smokers and nonwhite smokers. Early-emerging nicotine dependence is a promising marker for screening and interventions aimed at preventing smoking progression. PMID:27312479

  15. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP

    PubMed Central

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A.; Sumikawa, Katumi

    2014-01-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-d-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity. PMID:25545599

  16. Are Adolescent Smokers Addicted to Nicotine? The Suitability of the Nicotine Dependence Construct as Applied to Adolescents.

    ERIC Educational Resources Information Center

    Kassel, Jon D.

    2000-01-01

    Reviews the theoretical and empirical bases from which inferences regarding addictive smoking in adolescence can be drawn. It appears that although a significant proportion of teenage smokers do progress to dependence, this is not an inevitable outcome for all adolescent smokers. More research is needed in this area, specifically in measurement…

  17. Adolescents' movement towards cessation of smoking: role and relative value of the processes of change and nicotine dependence.

    PubMed

    Kleinjan, Marloes; van den Eijnden, Regina J J M; van Leeuwe, Jan; Brug, Johannes; van de Ven, Monique O M; Engels, Rutger C M E

    2008-01-01

    The present study addresses the applicability of the Transtheoretical Model's processes of change in explaining adolescents' readiness to quit smoking. Furthermore, the association between nicotine dependence and readiness to quit was assessed both directly, as well as indirectly through the processes of change. A cross-sectional survey was conducted, identifying 1547 weekly smokers aged 14-18 years. Structural equation modelling showed that the processes of change were only marginally associated with readiness to quit. Adding nicotine dependence to the model showed a direct association between nicotine dependence and readiness to quit. Only one process of change, self-liberation (i.e. choice/commitment to change and belief in the ability to change), was found to mediate this association. Nicotine dependence appeared to be highly important in adolescents' readiness to quit.

  18. Adolescent nicotine-induced dendrite remodeling in the nucleus accumbens is rapid, persistent, and D1-dopamine receptor dependent.

    PubMed

    Ehlinger, D G; Bergstrom, H C; Burke, J C; Fernandez, G M; McDonald, C G; Smith, R F

    2016-01-01

    Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in 3D. Spine density was also measured at both time points. Our morphometric results show (1) the formation of new dendritic branches and spines 1 day following nicotine exposure, (2) new dendritic branches, but not spine density, remains relatively stable for at least 21 days, (3) the co-administration of SCH-23390 completely blocked nicotine-induced dendritic remodeling of MSNs at both early and late time points, suggesting the formation of new dendritic branches in response to nicotine is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Overall this study provides new insight into how nicotine influences the normal trajectory of adolescent brain development and demonstrates a persistent form of nicotine-induced neuroplasticity in the NAcc shell that develops rapidly and is D1DR dependent.

  19. Approximating a Giving Up Smoking Dynamic on Adolescent Nicotine Dependence in Fractional Order

    PubMed Central

    2016-01-01

    In this work, we consider giving up smoking dynamic on adolescent nicotine dependence. First, we use the Caputo derivative to develop the model in fractional order. Then we apply two different numerical methods to compute accurate approximate solutions of this new model in fractional order and compare their results. In order to do this, we consider the generalized Euler method (GEM) and multi-step generalized differential transform method (MSGDTM). We also show the unique positive solution for this model and present numerical results graphically. PMID:27105426

  20. Approximating a Giving Up Smoking Dynamic on Adolescent Nicotine Dependence in Fractional Order.

    PubMed

    Zeb, Anwar; Zaman, Gul; Erturk, Vedat Suat; Alzalg, Baha; Yousafzai, Faisal; Khan, Madad

    2016-01-01

    In this work, we consider giving up smoking dynamic on adolescent nicotine dependence. First, we use the Caputo derivative to develop the model in fractional order. Then we apply two different numerical methods to compute accurate approximate solutions of this new model in fractional order and compare their results. In order to do this, we consider the generalized Euler method (GEM) and multi-step generalized differential transform method (MSGDTM). We also show the unique positive solution for this model and present numerical results graphically. PMID:27105426

  1. Assessment of nicotine dependence symptoms in adolescents: a comparison of five indicators

    PubMed Central

    O'Loughlin, J; DiFranza, J; Tarasuk, J; Meshefedjian, G; McMillan-Davey, E; Paradis, G; Tyndale, R; Clarke, P; Hanley, J

    2002-01-01

    Objective: To examine the psychometric properties, test-retest reliability, and convergent construct validity of five indicators of nicotine dependence (ND) symptoms in adolescents. Design: Analysis of baseline data from a prospective study on the natural history of ND in 1264 adolescents aged 12–13 years. Setting: Ten Montreal high schools. Subjects: 233 grade 7 students who had smoked cigarettes one or more times in the three months preceding the baseline data collection. Main outcome measures: Five indicators of ND symptoms including two that are multi-dimensional (a proxy measure of ICD-10 criteria for tobacco dependence; the Hooked on Nicotine Checklist (HONC)) and three new indicators of "symptom clusters" that emerged from principal component analysis (ND/cravings, withdrawal symptoms, self medication). Results: All five indicators demonstrated acceptable internal and test-retest reliability. The correlation between the HONC and ND/cravings was 0.910. All other correlations between indicators ranged between 0.716–0.824. There was considerable overlap in the independent correlates identified for each indicator. Conclusions: All five indicators performed well psychometrically. Until the meaning, relative importance, and usefulness of each scale is clarified in longitudinal work, decisions regarding which scale(s) are most informative will depend more on the content of the scales, the need for a multi- or unidimensional indicator, and whether or not the scale is theory based. PMID:12432161

  2. Nicotine-Dependence-Varying Effects of Smoking Events on Momentary Mood Changes among Adolescents

    PubMed Central

    Selya, Arielle S.; Updegrove, Nicole; Rose, Jennifer S.; Dierker, Lisa; Tan, Xianming; Hedeker, Donald; Li, Runze; Mermelstein, Robin J.

    2014-01-01

    Introduction Theories of nicotine addiction emphasize the initial role of positive reinforcement in the development of regular smoking behavior, and the role of negative reinforcement at later stages. These theories are tested here by examining the effects of amount smoked per smoking event on smoking-related mood changes, and how nicotine dependence (ND) moderates this effect. The current study examines these questions within a sample of light adolescent smokers drawn from the metropolitan Chicago area (N=151, 55.6% female, mean 17.7 years). Instruments Ecological momentary assessment data were collected via handheld computers, and additional variables were drawn from a traditional questionnaire. Methods Effects of the amount smoked per event on changes in positive affect (PA) and negative affect (NA) after vs. before smoking were examined, while controlling for subject-averaged amount smoked, age, gender, and day of week. ND-varying effects were examined using varying effect models to elucidate their change across levels of ND. Results The effect of the amount smoked per event was significantly associated with an increase in PA among adolescents with low-to-moderate levels of ND, and was not significant at high ND. Conversely, the effect of the amount smoked was significantly associated with a decrease in NA only for adolescents with low levels of ND, Conclusions These findings support that the role of positive reinforcement in early stages of dependent smoking, but do not support the role of negative reinforcement beyond early stages of smoking. Other potential contributing factors to the relationship between smoking behavior and PA/NA change are discussed. PMID:25306388

  3. Adolescent nicotine dependence symptom profiles and risk for future daily smoking.

    PubMed

    Rose, Jennifer S; Lee, Chien-Ti; Dierker, Lisa C; Selya, Arielle S; Mermelstein, Robin J

    2012-10-01

    Recent research on adolescent smokers suggests that there are important differences in the types of nicotine dependence (ND) symptoms that emerge and different patterns of ND symptoms. The purpose of this study was to use data from the longitudinal Social and Emotional Contexts of Adolescent Smoking Patterns Study to identify latent subgroups of adolescent experimental and nondaily smokers varying in number and types of endorsed ND symptoms. Profiles were identified using baseline level of smoking, individual patterns of ND symptoms and other ND risk factors. Discrete time survival analysis was used to examine profile differences in probability of becoming daily smokers 48 months later. Four distinct subgroups of smokers with different patterns of smoking behavior, ND symptoms, and alcohol and other substance use emerged. Heavier smoking adolescents with high symptom endorsement, particularly the need to smoke in the morning, were most likely to become daily smokers 48 months later. A subgroup of social smokers had high smoking exposure and symptom endorsement (except need to smoke in the morning), and high levels of other substance use. Despite lower rates of smoking frequency and quantity compared to the heavier smoking class, 36% of these adolescents smoked daily by 48 months, with a steeper decline in survival rates compared to other lighter smoking classes. Morning smoking symptoms and symptoms prioritizing smoking (i.e., choosing to spend money on cigarettes instead of lunch or smoking when ill or where smoking is forbidden) might quickly identify adolescent non-daily smokers with more severe dependence and higher risk for daily smoking. A focus on skills for avoiding social situations involving use of alcohol and other drugs and reducing peer smoking influences may be an important focus for reducing smoking and other substance use among social smokers. PMID:22673155

  4. Prevalence and correlates of heavy smoking and nicotine dependence in adolescents with bipolar and cannabis use disorders.

    PubMed

    Heffner, Jaimee L; Anthenelli, Robert M; Adler, Caleb M; Strakowski, Stephen M; Beavers, Jennifer; DelBello, Melissa P

    2013-12-30

    The study examined the prevalence and correlates of heavy smoking and nicotine dependence in adolescents with bipolar and cannabis use disorders. Participants were 80 adolescents between 13 and 22 years of age with co-occurring bipolar I disorder and cannabis abuse or dependence who reported ever trying a cigarette. Diagnostic and symptom severity measures were completed as part of the baseline assessments for a clinical trial. Almost half (49%) of these participants who ever tried a cigarette were current heavy smokers (≥10 cigarettes/day), and 70% met DSM-IV-TR lifetime criteria for nicotine dependence. Heavy smoking was associated with older age, heavier marijuana use and greater compulsive craving, lifetime diagnoses of attention-deficit/hyperactivity disorder, conduct disorder, illicit drug use disorders, and poorer overall functioning. Nicotine dependence was related to White race, higher current mania severity, and poorer overall functioning. These findings suggest that heavy smoking and nicotine dependence were highly prevalent among these adolescents. Although both were associated with greater physical and psychosocial problems, only heavy smoking was linked to a clear pattern of more severe substance-related and psychiatric problems. Further research to elucidate mechanisms and develop interventions to address early, entrenched patterns of co-use of tobacco and marijuana is warranted.

  5. Genetic Variants and Early Cigarette Smoking and Nicotine Dependence Phenotypes in Adolescents

    PubMed Central

    O'Loughlin, Jennifer; Sylvestre, Marie-Pierre; Labbe, Aurélie; Low, Nancy C.; Roy-Gagnon, Marie-Hélène; Dugas, Erika N.; Karp, Igor; Engert, James C.

    2014-01-01

    Background While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes. Methods In a prospective study of 1294 adolescents aged 12–13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7–8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator). Results The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076. Conclusions Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3). Impact Dopaminergic pathways may be salient during early smoking and the

  6. Nicotine and the adolescent brain

    PubMed Central

    Yuan, Menglu; Cross, Sarah J; Loughlin, Sandra E; Leslie, Frances M

    2015-01-01

    Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse. PMID:26018031

  7. Nicotine and the adolescent brain.

    PubMed

    Yuan, Menglu; Cross, Sarah J; Loughlin, Sandra E; Leslie, Frances M

    2015-08-15

    Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse. PMID:26018031

  8. Nicotine administration enhances negative occasion setting in adolescent rats.

    PubMed

    Meyer, Heidi C; Chodakewitz, Molly I; Bucci, David J

    2016-04-01

    Substantial research has established that exposure to nicotine during adolescence can lead to long-term changes in neural circuitry and behavior. However, relatively few studies have considered the effects of nicotine use on cognition during this critical stage of brain development. This is significant because the influence of nicotine on cognitive performance during adolescence may contribute to the development of regular nicotine use. For example, improvements in cognitive functioning may increase the perceived value of smoking and facilitate impulses to smoke. To address this, the present research tested the effects of nicotine on a form of inhibitory learning during adolescence. Specifically, adolescent rats were exposed to nicotine as they were trained in a negative occasion setting paradigm, in which successful performance depends on learning the conditions under which it is, or is not, appropriate to respond to a target stimulus. Here, we found that nicotine administration enhances negative occasion setting in adolescents. In addition, nicotine increased the amount of orienting behavior directed toward the inhibitory stimulus, suggesting that improvements in this form of behavioral inhibition may be attributed to nicotine-induced increases in attentional processing. These results may help elucidate the factors that contribute to the onset as well as continued use of products containing nicotine during adolescence and provide insight to increase the effectiveness of interventions targeted at reducing the prevalence of adolescent smoking. PMID:26779671

  9. Adolescent nicotine exposure disrupts context conditioning in adulthood in rats.

    PubMed

    Spaeth, Andrea M; Barnet, Robert C; Hunt, Pamela S; Burk, Joshua A

    2010-10-01

    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.

  10. Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood.

    PubMed

    Slotkin, Theodore A; Bodwell, Bethany E; Ryde, Ian T; Seidler, Frederic J

    2008-05-15

    Nicotine alters the developmental trajectory of acetylcholine (ACh) systems in the immature brain, with vulnerability extending from fetal stages through adolescence. We administered nicotine to adolescent rats (postnatal days PN30-47) and then examined the subsequent response to nicotine given in adulthood (PN90-107), simulating plasma levels in smokers, and performing evaluations during nicotine treatment (PN105) and withdrawal (PN110, PN120 and PN130), as well as assessing persistent changes at 6 months of age (PN180). We measured nicotinic acetylcholine receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a marker for ACh terminals, and hemicholinium-3 (HC3) binding to the choline transporter, an index of ACh presynaptic activity. By itself, adolescent nicotine exposure evoked sex-selective deficits in cerebrocortical HC3 binding while elevating ChAT in young adulthood in striatum and midbrain. Nicotine given in adulthood produced profound nAChR upregulation lasting 2 weeks after discontinuing treatment, and decrements in cerebrocortical and striatal HC3 binding emerged during withdrawal, indicative of reduced ACh synaptic activity. For all three parameters, adolescent nicotine altered the responses to nicotine given in adulthood, producing both sensitization and desensitization that depended on sex and brain region, effects that parallel the disparate behavioral outcomes reported for these treatments. The interaction seen here for the impact of adolescent nicotine exposure on adult nicotine responses was substantially greater than that found previously for the effects of prenatal nicotine exposure on adult responses. Our findings thus reinforce the importance of adolescence as a critical period in which the future responsiveness to nicotine is programmed.

  11. Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood.

    PubMed

    Slotkin, Theodore A; Bodwell, Bethany E; Ryde, Ian T; Seidler, Frederic J

    2008-05-15

    Nicotine alters the developmental trajectory of acetylcholine (ACh) systems in the immature brain, with vulnerability extending from fetal stages through adolescence. We administered nicotine to adolescent rats (postnatal days PN30-47) and then examined the subsequent response to nicotine given in adulthood (PN90-107), simulating plasma levels in smokers, and performing evaluations during nicotine treatment (PN105) and withdrawal (PN110, PN120 and PN130), as well as assessing persistent changes at 6 months of age (PN180). We measured nicotinic acetylcholine receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a marker for ACh terminals, and hemicholinium-3 (HC3) binding to the choline transporter, an index of ACh presynaptic activity. By itself, adolescent nicotine exposure evoked sex-selective deficits in cerebrocortical HC3 binding while elevating ChAT in young adulthood in striatum and midbrain. Nicotine given in adulthood produced profound nAChR upregulation lasting 2 weeks after discontinuing treatment, and decrements in cerebrocortical and striatal HC3 binding emerged during withdrawal, indicative of reduced ACh synaptic activity. For all three parameters, adolescent nicotine altered the responses to nicotine given in adulthood, producing both sensitization and desensitization that depended on sex and brain region, effects that parallel the disparate behavioral outcomes reported for these treatments. The interaction seen here for the impact of adolescent nicotine exposure on adult nicotine responses was substantially greater than that found previously for the effects of prenatal nicotine exposure on adult responses. Our findings thus reinforce the importance of adolescence as a critical period in which the future responsiveness to nicotine is programmed. PMID:18395624

  12. Nicotine dependence and psychiatric disorders.

    PubMed

    Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

    2003-01-01

    Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention

  13. Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors.

    PubMed

    Mateos, B; Borcel, E; Loriga, R; Luesu, W; Bini, V; Llorente, R; Castelli, M P; Viveros, M-P

    2011-12-01

    We have analysed the long-term effects of adolescent (postnatal day 28-43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB(1) cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB(1) receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB(1) and nicotinic receptors.

  14. Long-term, low-level adolescent nicotine exposure produces dose-dependent changes in cocaine sensitivity and reward in adult mice.

    PubMed

    Kelley, Brian M; Rowan, James D

    2004-01-01

    Cigarette smoking by adolescents is a strong predictor of future drug use, abuse, and dependence. While this "gateway drug effect" is assumed to be related to psychosocial factors, data from our laboratory suggests that adolescent nicotine use may permanently disrupt reward systems through changes in dopamine receptor function. Behavioral pharmacological methods known to be indirectly (motor activity) and directly (conditioned-place-preference) related to drug reinforcement were used to examine changes in cocaine sensitivity. Testing was performed on adult mice that were exposed to nicotine (0.3, 1.0, and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during adolescence (postnatal days 25-57). Prior to testing, subjects had a 28 day drug-free, time-off period. After acclimation to the testing apparatus, the locomotor effects (30 min, 30 cm traveled) of cocaine (5, 10, and 20 mg/kg, IP) were measured daily; cocaine tests were preceded and followed by saline control tests. Following the acute dose-response curve, mice received saline followed by 5 days of 20.0 mg/kg cocaine. Thereafter, mice underwent condition-place-preference testing. A pre-test was performed to determine compartment preference (i.e., no injection, 20 min test). Cocaine (10 mg/kg, IP) was paired with the subjects non-preferred side and saline with the other. Conditioning sessions were conducted for 8 days with the order of drug/saline injections counter-balanced across subjects. A drug-free, post-test occurred on the day following the final conditioning session. A dose-dependent relationship between adolescent nicotine exposure and cocaine reward was noted in the adult mice across both test conditions. Subjects exposed to nicotine showed an increased response to cocaine's motor activating effects and a decreased response to cocaine's rewarding effects. A follow-up study was undertaken to evaluate dopamine D1, D2, and D3 receptor function in adult mice exposed to the highest dose of nicotine from the first

  15. Nicotine dependence and smoking cessation.

    PubMed

    Tan, Linxiang; Tang, Quansheng; Hao, Wei

    2009-11-01

    Tobacco use is the single most preventable cause of death, disability and disease in the world and is projected to be the leading cause of death and disability across all developed and developing countries by 2020. Nicotine, the primary active ingredient of cigarettes that contributes to physical dependence, acts on nicotine receptors in the central nervous system and leads to the release of neurotransmitters (such as dopamine). Like other drugs of abuse, nicotine is thought to produce reinforcing effect by activating the mesocorticolimbic dopamine system. A wide variety of cessation treatments of nicotine dependence is commercially available, yet only 2 general approaches have received empirical validation: behavioral intervention (including 5 As brief intervention) and pharmacotherapy. The evidences show that 5 As brief intervention is one of the most cost-effective treatments in clinical work for busy physicians. Three types of medications have been available in market for smoking cessation treatment: nicotine replacement treatment (NRT, i.e., transdermal patch, gum, inhaler, nasal spray, and lozenge), sustained release bupropion and varenicline. Varenicline, a novel alpha4beta2 nicotinic receptor partial agonist, is effective for tobacco dependence. Phase III trials suggest that it is more effective than NRT and bupropion SR. The safety profile of varenicline is excellent, with the most commonly occurring adverse events, nausea, typically mild and well tolerated. However, new safety warnings are added to the varenicline label because of post-marketing report including agitation, depression and suicidality. A causal connection between varenicline use and these symptoms has not been established. PMID:19952392

  16. Genetics of Nicotine Dependence and Pharmacotherapy

    PubMed Central

    Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.

    2008-01-01

    Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884

  17. Nicotine, adolescence, and stress: A review of how stress can modulate the negative consequences of adolescent nicotine abuse.

    PubMed

    Holliday, Erica; Gould, Thomas J

    2016-06-01

    In order to continue the decline of smoking prevalence, it is imperative to identify factors that contribute to the development of nicotine and tobacco addiction, such as adolescent initiation of nicotine use, adolescent stress, and their interaction. This review highlights the biological differences between adolescent and adults in nicotine use and resulting effects, and examines the enduring consequences of adolescent nicotine administration. A review of both clinical and preclinical literature indicates that adolescent, but not adult, nicotine administration leads to increased susceptibility for development of long-lasting impairments in learning and affect. Finally, the role stress plays in normal adolescent development, the deleterious effects stress has on learning and memory, and the negative consequences resulting from the interaction of stress and nicotine during adolescence is reviewed. The review concludes with ways in which future policies could benefit by addressing adolescent stress as a means of reducing adolescent nicotine abuse.

  18. An Integration of Parents’ and Best Friends’ Smoking, Smoking-Specific Cognitions, and Nicotine Dependence in Relation to Readiness to Quit Smoking: A Comparison between Adolescents with and without Asthma

    PubMed Central

    Engels, Rutger C. M. E.; Kleinjan, Marloes; van den Eijnden, Regina J. J. M.

    2008-01-01

    Objective To study the impact of parents’ and best friends’ smoking, nicotine dependence, and craving on smoking-specific cognitions, and readiness to quit in adolescents with and without asthma. Methods Structural equation analyses were applied to data from a sample of 1,120 daily smoking adolescents, 83 of whom had asthma. Results Adolescents with asthma felt more ready to quit, and cognitions were more strongly related to readiness to quit among adolescents with asthma than among adolescents without asthma. Moreover, best friends’ smoking seemed more relevant to the cognitions of adolescents with asthma. Nicotine dependence and craving were strongly related to cognitions, and to readiness to quit in both groups. The relation between craving and readiness to quit, however, was stronger among participants with asthma. Conclusions Reduction of nicotine dependence and craving is essential for both groups. Youth with asthma may benefit even more from cognitive-based cessation services than healthy youth. The finding that adolescents with asthma are relatively more ready to quit, and that their cognitions are more easily affected can be turned into advantages in asthma-specific cessation services. PMID:18287108

  19. Blockade of cholinergic transmission elicits somatic signs in nicotine-naïve adolescent rats

    PubMed Central

    Schmidt, Clare E.; Manbeck, Katherine E.; Shelley, David; Harris, Andrew C.

    2015-01-01

    High doses of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine can elicit somatic signs resembling those associated with nicotine withdrawal in nicotine-naïve adult rats. Understanding this phenomenon, and its possible modulation by acute nicotine and age, could inform the use of mecamylamine as both an experimental tool and potential pharmacotherapy for tobacco dependence and other disorders. This study evaluated the ability of high-dose mecamylamine to elicit somatic signs in adolescent rats, and the potential for acute nicotine pretreatment to potentiate this effect as previously reported in adults. Single or repeated injections of mecamylamine (1.5 or 3.0 mg/kg, s.c.) elicited somatic signs in nicotine-naïve adolescents, but this effect was not influenced by 2 h pretreatment with acute nicotine (0.5 mg/kg, s.c.). In an initial evaluation of the effects of age in this model, mecamylamine (2.25 mg/kg, s.c.) elicited somatic signs in nicotine-naïve adolescents and adults. This effect was modestly enhanced following acute nicotine injections in adults but not in adolescents, even when a higher nicotine dose (1.0 rather than 0.5 mg/kg, s.c.) was used in adolescents to account for age differences in nicotine pharmacokinetics. These studies are the first to show that mecamylamine elicits somatic signs in nicotine-naïve adolescent rats, an effect that should be considered when designing and interpreting studies examining effects of high doses of mecamylamine in adolescents. Our findings also provide preliminary evidence that these signs may be differentially modulated by acute nicotine pretreatment in adolescents versus adults. PMID:26539119

  20. Early adolescent nicotine exposure affects later-life cocaine reward in mice.

    PubMed

    Alajaji, Mai; Lazenka, Matthew F; Kota, Dena; Wise, Laura E; Younis, Rabha M; Carroll, F Ivy; Levine, Amir; Selley, Dana E; Sim-Selley, Laura J; Damaj, M Imad

    2016-06-01

    Adolescence represents a unique developmental period associated with increased risk-taking behavior and experimentation with drugs of abuse, in particular nicotine. We hypothesized that exposure to nicotine during early adolescence might increase the risk for drug reward in adulthood. To test this hypothesis, male ICR mice were treated with a subchronic regimen of nicotine or saline during adolescence, and their preference for cocaine, morphine and amphetamine was examined using the conditioned place preference (CPP) test in adulthood. Long-term behavioral changes induced by nicotine suggested a possible role of altered gene transcription. Thus, immunoblot for ΔFosB, a member of the Fos family of transcription factors, was conducted in the nucleus accumbens of these mice. Mice treated with nicotine during early but not late adolescence showed an increase in CPP for cocaine, morphine and amphetamine later in adulthood. This effect was not seen in mice pretreated with a subchronic regimen of nicotine as adults, suggesting that exposure to nicotine specifically during early adolescence increases the rewarding effects of other drugs in adulthood. However, adolescent nicotine exposure did not alter highly palatable food conditioning in mice. The enhancement of cocaine CPP by nicotine was strain-dependent and was blocked by pretreatment with nicotinic antagonists. In addition, nicotine exposure during early adolescence induced ΔFosB expression to a greater extent than identical nicotine exposure in adulthood, and enhanced cocaine-induced locomotor sensitization later in adulthood. These results suggest that nicotine exposure during early adolescence increases drug-induced reward in adulthood through mechanisms that may involve the induction of ΔFosB. PMID:26808314

  1. Cigarette smoking, nicotine dependence, and treatment.

    PubMed Central

    Sees, K L

    1990-01-01

    Since the 1988 Surgeon General's report on nicotine addiction, more attention is being given to nicotine dependence as a substantial contributing factor in cigarette smokers' inability to quit. Many new medications are being investigated for treating nicotine withdrawal and for assisting in long-term smoking abstinence. Medications alone probably will not be helpful; they should be used as adjuncts in comprehensive smoking abstinence programs that address not only the physical dependence on nicotine but also the psychological dependence on cigarette smoking. PMID:2190425

  2. The genetics of nicotine dependence.

    PubMed

    Li, Ming D

    2006-04-01

    Despite almost two decades of intensive tobacco-control efforts, approximately 23% of American adults continue to smoke, and 13% are nicotine-dependent. Cigarette smoking is the greatest preventable cause of cancer, accounting for at least 30% of all cancer deaths and 87% of lung cancer deaths. Smoking behavior is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that the heritability of liability for nicotine dependence (ND) is at least 50%. During the past several years, significant efforts have been made to identify susceptibility genes for ND using both genome-wide linkage and association analysis approaches. It is expected that identification of susceptibility genes for ND will allow the development and tailoring of both prevention strategies for individuals at risk and effective treatment programs and medicines for individuals who use tobacco products. This review summarizes the recent progress in genetic studies of ND. As genotyping technology is being improved and well-characterized clinical samples on smoking behavior become available, more and more genes and genetic variants responsible for ND will be identified in the near future. PMID:16539894

  3. Frequent Marijuana Use is Associated with Greater Nicotine Addiction in Adolescent Smokers

    PubMed Central

    Rubinstein, Mark L.; Rait, Michelle A.; Prochaska, Judith J.

    2014-01-01

    BACKGROUND Marijuana and tobacco are the substances used most commonly by adolescents and co-occurring use is common. Use of one substance may potentiate the addictive properties of the other. The current study examined the severity of nicotine addiction among teen smokers as a function of co-occurring marijuana use. METHODS Participants were 165 adolescents (13–17 years old) who reported smoking at least 1 cigarette per day (CPD) in the past 30 days. General linear models examined the association of marijuana use with multiple measures of nicotine addiction including the Modified Fagerström Tolerance Questionnaire (mFTQ), Hooked on Nicotine Checklist (HONC), ICD-10, and the Nicotine Dependence Syndrome Scale (NDSS). RESULTS The adolescent sample (mean age=16.1 years, SD=0.95) averaged 3.0 CPD (SD=3.0) for 1.98 years (SD=1.5). Most (79.5%) also smoked marijuana in the past 30 days. In models controlling for age, daily smoking status, and years of tobacco smoking, frequency of marijuana use accounted for 25–44% of the variance for all four measures of adolescent nicotine dependence. CONCLUSIONS Marijuana use was associated with greater reported nicotine addiction among adolescent smokers. The findings suggest a role of marijuana in potentiating nicotine addiction and underscore the need for treatments that address both smoked substances. PMID:24928480

  4. Changes in Genetic and Environmental Influences on the Development of Nicotine Dependence and Major Depressive Disorder from Middle Adolescence to Early Adulthood

    PubMed Central

    Tully, Erin C.; Iacono, William G.; McGue, Matt

    2010-01-01

    This longitudinal study used a representative community sample of same-sex twins (485 MZ pairs, 271 DZ pairs) to study longitudinal changes in genetic and environmental influences on nicotine dependence (NicD) symptoms and major depressive disorder (MDD) symptoms and the longitudinal relationships between NicD and MDD symptoms at three relatively discrete ages spanning middle adolescence to early adulthood (ages 15, 18, and 21). Clinical interviews were used to assess NicD and MDD symptoms lifetime at age 15 and during the previous three years at the two subsequent assessments. Biometric models revealed similar patterns of findings for NicD and MDD. Heritability increased with age, particularly between ages 15 and 18. Shared environmental influences were small, and the proportion of variance attributed to shared environmental influences decreased with age. Nonshared environmental influences were moderate to large in magnitude and were entirely age-specific. Both NicD and MDD symptoms showed considerable stability from age 15 to 21, and at each age those with one disorder showed elevated rates of the other. However, a cross-lagged model revealed no longitudinal predictive relationships between MDD symptoms and NicD symptoms after accounting for stability of symptoms within disorders. In summary, the transition between middle and late adolescence is a critical period for developmental shifts in the magnitudes of genetic and environmental influences on both MDD and NicD symptoms. Despite similarities in the development of genetic and environmental influences for the two phenotypes, the association between NicD and MDD reflects concurrent covariation rather than one phenotype being an antecedent influence on the subsequent development of the other. PMID:20883585

  5. Full-gestational exposure to nicotine and ethanol augments nicotine self-administration by altering ventral tegmental dopaminergic function due to NMDA receptors in adolescent rats.

    PubMed

    Roguski, Emily E; Sharp, Burt M; Chen, Hao; Matta, Shannon G

    2014-03-01

    In adult rats, we have shown full-gestational exposure to nicotine and ethanol (Nic + EtOH) augmented nicotine self-administration (SA) (increased nicotine intake) compared to pair-fed (PF) offspring. Therefore, we hypothesized that full-gestational exposure to Nic + EtOH disrupts control of dopaminergic (DA) circuitry by ventral tegmental area (VTA) NMDA receptors, augmenting nicotine SA and DA release in nucleus accumbens (NAcc) of adolescents. Both NAcc DA and VTA glutamate release were hyper-responsive to intra-VTA NMDA in Nic + EtOH offspring versus PF (p = 0.03 and 0.02, respectively). Similarly, DA release was more responsive to i.v. nicotine in Nic + EtOH offspring (p = 0.02). Local DL-2-Amino-5-phosphonopentanoic acid sodium salt (AP5) (NMDA receptor antagonist) infusion into the VTA inhibited nicotine-stimulated DA release in Nic + EtOH and PF offspring. Nicotine SA was augmented in adolescent Nic + EtOH versus PF offspring (p = 0.000001). Daily VTA microinjections of AP5 reduced nicotine SA by Nic + EtOH offspring, without affecting PF (p = 0.000032). Indeed, nicotine SA in Nic + EtOH offspring receiving AP5 was not different from PF offspring. Both VTA mRNA transcripts and NMDA receptor subunit proteins were not altered in Nic + EtOH offspring. In summary, adolescent offspring exposed to gestational Nic + EtOH show markedly increased vulnerability to become dependent on nicotine. This reflects the enhanced function of a subpopulation of VTA NMDA receptors that confer greater nicotine-induced DA release in NAcc. We hypothesized that concurrent gestational exposure to nicotine and ethanol would disrupt the control of VTA dopaminergic circuitry by NMDA receptors. Resulting in the augmented nicotine self-administration (SA) in adolescent offspring.

  6. Drug-dependent behaviors and nicotinic acetylcholine receptor expressions in Caenorhabditis elegans following chronic nicotine exposure.

    PubMed

    Polli, Joseph R; Dobbins, Dorothy L; Kobet, Robert A; Farwell, Mary A; Zhang, Baohong; Lee, Myon-Hee; Pan, Xiaoping

    2015-03-01

    Nicotine, the major psychoactive compound in tobacco, targets nicotinic acetylcholine receptors (nAChRs) and results in drug dependence. The nematode Caenorhabditis elegans' (C. elegans) genome encodes conserved and extensive nicotinic receptor subunits, representing a useful system to investigate nicotine-induced nAChR expressions in the context of drug dependence. However, the in vivo expression pattern of nAChR genes under chronic nicotine exposure has not been fully investigated. To define the role of nAChR genes involved in nicotine-induced locomotion changes and the development of tolerance to these effects, we characterized the locomotion behavior combining the use of two systems: the Worm Tracker hardware and the WormLab software. Our results indicate that the combined system is an advantageous alternative to define drug-dependent locomotion behavior in C. elegans. Chronic (24-h dosing) nicotine exposure at 6.17 and 61.7μM induced nicotine-dependent behaviors, including drug stimulation, tolerance/adaption, and withdrawal responses. Specifically, the movement speed of naïve worms on nicotine-containing environments was significantly higher than on nicotine-free environments, suggesting locomotion stimulation by nicotine. In contrast, the 24-h 6.17μM nicotine-treated worms exhibited significantly higher speeds on nicotine-free plates than on nicotine-containing plates. Furthermore significantly increased locomotion behavior during nicotine cessation was observed in worms treated with a higher nicotine concentration of 61.7μM. The relatively low locomotion speed of nicotine-treated worms on nicotine-containing environments also indicates adaption/tolerance of worms to nicotine following chronic nicotine exposure. In addition, this study provides useful information regarding the comprehensive in vivo expression profile of the 28 "core" nAChRs following different dosages of chronic nicotine treatments. Eleven genes (lev-1, acr-6, acr-7, acr-11, lev-8, acr

  7. Negative affective states and cognitive impairments in nicotine dependence.

    PubMed

    Hall, F Scott; Der-Avakian, Andre; Gould, Thomas J; Markou, Athina; Shoaib, Mohammed; Young, Jared W

    2015-11-01

    Smokers have substantial individual differences in quit success in response to current treatments for nicotine dependence. This observation may suggest that different underlying motivations for continued tobacco use across individuals and nicotine cessation may require different treatments in different individuals. Although most animal models of nicotine dependence emphasize the positive reinforcing effects of nicotine as the major motivational force behind nicotine use, smokers generally report that other consequences of nicotine use, including the ability of nicotine to alleviate negative affective states or cognitive impairments, as reasons for continued smoking. These states could result from nicotine withdrawal, but also may be associated with premorbid differences in affective and/or cognitive function. Effects of nicotine on cognition and affect may alleviate these impairments regardless of their premorbid or postmorbid origin (e.g., before or after the development of nicotine dependence). The ability of nicotine to alleviate these symptoms would thus negatively reinforce behavior, and thus maintain subsequent nicotine use, contributing to the initiation of smoking, the progression to dependence and relapse during quit attempts. The human and animal studies reviewed here support the idea that self-medication for pre-morbid and withdrawal-induced impairments may be more important factors in nicotine addiction and relapse than has been previously appreciated in preclinical research into nicotine dependence. Given the diverse beneficial effects of nicotine under these conditions, individuals might smoke for quite different reasons. This review suggests that inter-individual differences in the diverse effects of nicotine associated with self-medication and negative reinforcement are an important consideration in studies attempting to understand the causes of nicotine addiction, as well as in the development of effective, individualized nicotine cessation

  8. Negative affective states and cognitive impairments in nicotine dependence.

    PubMed

    Hall, F Scott; Der-Avakian, Andre; Gould, Thomas J; Markou, Athina; Shoaib, Mohammed; Young, Jared W

    2015-11-01

    Smokers have substantial individual differences in quit success in response to current treatments for nicotine dependence. This observation may suggest that different underlying motivations for continued tobacco use across individuals and nicotine cessation may require different treatments in different individuals. Although most animal models of nicotine dependence emphasize the positive reinforcing effects of nicotine as the major motivational force behind nicotine use, smokers generally report that other consequences of nicotine use, including the ability of nicotine to alleviate negative affective states or cognitive impairments, as reasons for continued smoking. These states could result from nicotine withdrawal, but also may be associated with premorbid differences in affective and/or cognitive function. Effects of nicotine on cognition and affect may alleviate these impairments regardless of their premorbid or postmorbid origin (e.g., before or after the development of nicotine dependence). The ability of nicotine to alleviate these symptoms would thus negatively reinforce behavior, and thus maintain subsequent nicotine use, contributing to the initiation of smoking, the progression to dependence and relapse during quit attempts. The human and animal studies reviewed here support the idea that self-medication for pre-morbid and withdrawal-induced impairments may be more important factors in nicotine addiction and relapse than has been previously appreciated in preclinical research into nicotine dependence. Given the diverse beneficial effects of nicotine under these conditions, individuals might smoke for quite different reasons. This review suggests that inter-individual differences in the diverse effects of nicotine associated with self-medication and negative reinforcement are an important consideration in studies attempting to understand the causes of nicotine addiction, as well as in the development of effective, individualized nicotine cessation

  9. Can one puff really make an adolescent addicted to nicotine? A critical review of the literature

    PubMed Central

    2010-01-01

    Rationale In the past decade, there have been various attempts to understand the initiation and progression of tobacco smoking among adolescents. One line of research on these issues has made strong claims regarding the speed in which adolescents can become physically and mentally addicted to smoking. According to these claims, and in contrast to other models of smoking progression, adolescents can lose autonomy over their smoking behavior after having smoked one puff in their lifetime and never having smoked again, and can become mentally and physically "hooked on nicotine" even if they have never smoked a puff. Objectives To critically examine the conceptual and empirical basis for the claims made by the "hooked on nicotine" thesis. Method We reviewed the major studies on which the claims of the "hooked on nicotine" research program are based. Results The studies we reviewed contained substantive conceptual and methodological flaws. These include an untenable and idiosyncratic definition of addiction, use of single items or of very lenient criteria for diagnosing nicotine dependence, reliance on responders' causal attributions in determining physical and mental addiction to nicotine and biased coding and interpretation of the data. Discussion The conceptual and methodological problems detailed in this review invalidate many of the claims made by the "hooked on nicotine" research program and undermine its contribution to the understanding of the nature and development of tobacco smoking in adolescents. PMID:21067587

  10. Prenatal Alcohol Exposure Increases Postnatal Acceptability of Nicotine Odor and Taste in Adolescent Rats

    PubMed Central

    Mantella, Nicole M.; Youngentob, Steven L.

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  11. Nicotine-induced place conditioning and locomotor activity in an adolescent animal model of attention deficit/hyperactivity disorder (ADHD).

    PubMed

    Watterson, Elizabeth; Daniels, Carter W; Watterson, Lucas R; Mazur, Gabriel J; Brackney, Ryan J; Olive, M Foster; Sanabria, Federico

    2015-09-15

    Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

  12. Electronic cigarettes and nicotine dependence: evolving products, evolving problems.

    PubMed

    Cobb, Caroline O; Hendricks, Peter S; Eissenberg, Thomas

    2015-05-21

    Electronic cigarettes (ECIGs) use an electric heater to aerosolize a liquid that usually contains propylene glycol, vegetable glycerin, flavorants, and the dependence-producing drug nicotine. ECIG-induced nicotine dependence has become an important concern, as some ECIGs deliver very little nicotine while some may exceed the nicotine delivery profile of a tobacco cigarette. This variability is relevant to tobacco cigarette smokers who try to switch to ECIGs. Products with very low nicotine delivery may not substitute for tobacco cigarettes, so that ECIG use is accompanied by little reduced risk of cigarette-caused disease. Products with very high nicotine delivery may make quitting ECIGs particularly difficult should users decide to try. For non-smokers, the wide variability of ECIGs on the market is especially troublesome: low nicotine products may lead them to initiate nicotine self-administration and progress to higher dosing ECIGs or other products, and those that deliver more nicotine may produce nicotine dependence where it was not otherwise present. External regulatory action, guided by strong science, may be required to ensure that population-level nicotine dependence does not rise.

  13. Adolescent nicotine exposure fails to impact cocaine reward, aversion and self-administration in adult male rats.

    PubMed

    Pomfrey, Rebecca L; Bostwick, Tamaara A; Wetzell, B Bradley; Riley, Anthony L

    2015-10-01

    The present experiments examined the effects of adolescent nicotine pre-exposure on the rewarding and aversive effects of cocaine and on cocaine self-administration in adult male rats. In Experiment 1, adolescent Sprague-Dawley rats (postnatal days 28-43) were given once daily injections of nicotine (0.6mg/kg) or vehicle and then tested for the aversive and rewarding effects of cocaine in a combined conditioned taste avoidance (CTA)/conditioned place preference (CPP) procedure in adulthood. In Experiment 2, adolescent Sprague-Dawley rats were pre-exposed to nicotine then tested for cocaine self-administration (0.25 or 0.75mg/kg), progressive ratio (PR) responding, extinction and cue-induced reinstatement in adulthood. In Experiment 1, rats showed significant dose-dependent cocaine-induced taste avoidance with cocaine-injected subjects consuming less saccharin over trials, but no effect of nicotine pre-exposure. For place preferences, cocaine induced significant place preferences with cocaine injected subjects spending significantly more time on the cocaine-paired side, but again there was no effect of nicotine history. All rats in Experiment 2 showed clear, dose-dependent responding during cocaine acquisition, PR testing, extinction and reinstatement with no effect of nicotine pre-exposure. These studies demonstrate that adolescent nicotine pre-exposure does not have an impact on cocaine's affective properties or its self-administration at least with the specific parametric conditions under which these effects were tested.

  14. Adolescent nicotine exposure fails to impact cocaine reward, aversion and self-administration in adult male rats.

    PubMed

    Pomfrey, Rebecca L; Bostwick, Tamaara A; Wetzell, B Bradley; Riley, Anthony L

    2015-10-01

    The present experiments examined the effects of adolescent nicotine pre-exposure on the rewarding and aversive effects of cocaine and on cocaine self-administration in adult male rats. In Experiment 1, adolescent Sprague-Dawley rats (postnatal days 28-43) were given once daily injections of nicotine (0.6mg/kg) or vehicle and then tested for the aversive and rewarding effects of cocaine in a combined conditioned taste avoidance (CTA)/conditioned place preference (CPP) procedure in adulthood. In Experiment 2, adolescent Sprague-Dawley rats were pre-exposed to nicotine then tested for cocaine self-administration (0.25 or 0.75mg/kg), progressive ratio (PR) responding, extinction and cue-induced reinstatement in adulthood. In Experiment 1, rats showed significant dose-dependent cocaine-induced taste avoidance with cocaine-injected subjects consuming less saccharin over trials, but no effect of nicotine pre-exposure. For place preferences, cocaine induced significant place preferences with cocaine injected subjects spending significantly more time on the cocaine-paired side, but again there was no effect of nicotine history. All rats in Experiment 2 showed clear, dose-dependent responding during cocaine acquisition, PR testing, extinction and reinstatement with no effect of nicotine pre-exposure. These studies demonstrate that adolescent nicotine pre-exposure does not have an impact on cocaine's affective properties or its self-administration at least with the specific parametric conditions under which these effects were tested. PMID:26255152

  15. Nicotine vaccines to treat tobacco dependence.

    PubMed

    Goniewicz, Maciej L; Delijewski, Marcin

    2013-01-01

    Tobacco smoking is globally far more widespread than use of any other substance of abuse. Nicotine is an important tobacco constituent that is responsible for addictive properties of smoking. The currently available medications for the treatment of nicotine addiction have limited efficacy. A challenging novel therapeutic concept is vaccination against nicotine. An efficient vaccine would generate antibodies that sequester nicotine in the blood and prevent its access to the brain. The vaccine would have great potential for treating nicotine addiction and for relapse prevention. We reviewed the current status of vaccines against nicotine addiction that are undergoing clinical trials or are in preclinical development. We discuss problems associated with the development of nicotine vaccines, their efficacy in addiction treatment, challenges and ethical concerns. Existing evidence indicates that nicotine vaccination is well tolerated and capable of inducing an immune response but its effectiveness in increasing smoking abstinence has not been shown so far.

  16. How Prepared Are Psychiatry Residents for Treating Nicotine Dependence?

    ERIC Educational Resources Information Center

    Prochaska, Judith J.; Fromont, Sebastien C.; Hall, Sharon M.

    2005-01-01

    Objective: Nicotine dependence is the most prevalent substance abuse disorder among adult psychiatric patients and a leading cause of death and disability. The authors examined the extent to which psychiatry residents are prepared to treat nicotine dependence in clinical practice. Methods: Residents from five psychiatry residency programs in…

  17. The acute effects of nicotine on positive and negative affect in adolescent smokers.

    PubMed

    Kassel, Jon D; Evatt, Daniel P; Greenstein, Justin E; Wardle, Margaret C; Yates, Marisa C; Veilleux, Jennifer C

    2007-08-01

    Although adolescent cigarette smoking remains a critical public health concern, little is known about the reinforcing mechanisms governing smoking in this vulnerable population. To assess predictions derived from both positive and negative reinforcement models of drug use, the authors measured the acute effects of nicotine, as administered via tobacco cigarettes, on both positive and negative affect in a group of 15- to 18-year-old smokers. A matched group of nonsmokers served as a comparison group. Findings revealed that whereas adolescents who smoked a cigarette experienced reductions in both positive and negative affect, the observed reductions in negative affect were moderated by nicotine content of the cigarette (high yield vs. denicotinized), level of nicotine dependence, level of baseline craving, and smoking expectancies pertinent to negative affect regulation. Nonsmokers experienced no change in affect over the 10-min assessment period, and no interaction effects were observed for positive affect. Overall, the findings conform to a negative reinforcement model of nicotine effects and strongly suggest that, even among young light smokers, nicotine dependence and resultant withdrawal symptomatology may serve as motivating factors governing smoking behavior.

  18. The acute effects of nicotine on positive and negative affect in adolescent smokers.

    PubMed

    Kassel, Jon D; Evatt, Daniel P; Greenstein, Justin E; Wardle, Margaret C; Yates, Marisa C; Veilleux, Jennifer C

    2007-08-01

    Although adolescent cigarette smoking remains a critical public health concern, little is known about the reinforcing mechanisms governing smoking in this vulnerable population. To assess predictions derived from both positive and negative reinforcement models of drug use, the authors measured the acute effects of nicotine, as administered via tobacco cigarettes, on both positive and negative affect in a group of 15- to 18-year-old smokers. A matched group of nonsmokers served as a comparison group. Findings revealed that whereas adolescents who smoked a cigarette experienced reductions in both positive and negative affect, the observed reductions in negative affect were moderated by nicotine content of the cigarette (high yield vs. denicotinized), level of nicotine dependence, level of baseline craving, and smoking expectancies pertinent to negative affect regulation. Nonsmokers experienced no change in affect over the 10-min assessment period, and no interaction effects were observed for positive affect. Overall, the findings conform to a negative reinforcement model of nicotine effects and strongly suggest that, even among young light smokers, nicotine dependence and resultant withdrawal symptomatology may serve as motivating factors governing smoking behavior. PMID:17696710

  19. Need for validation of Fagerstrom Test for Nicotine Dependence in Indian Context: Implications for Nicotine Replacement Therapy

    PubMed Central

    Sharma, Manoj Kumar; Sharma, Priyamvada

    2016-01-01

    Background: Variety of smokeable and chewable tobacco products with diverse nicotine content are used in India. Nicotine quantity in tobacco products has a direct bearing on developing tobacco dependence. The present work used this information to derive scores on the Fagerstrom test for nicotine dependence (FTND). It was used to determine the dosing of nicotine replacement treatment (NRT). Materials and Methods: Nicotine score quantitation was taken from the previous study. This data was applied to FTND to determine the relationship of nicotine content to the potential degree of dependence. Results: Application of nicotine quantitation to FTND in a hypothetical experiment significantly altered the scores from medium to high depending on the brand the used. Conclusion: Application of qunatitation of nicotine content in FTND score has implications for the assessment of tobacco dependence and NRT dose. The study implies validation of FTND using nicotine quantity in the consumed tobacco product as a scorable parameter in the FTND. PMID:27114620

  20. Familial and Non-Familial Smoking: Effects on Smoking and Nicotine Dependence

    PubMed Central

    Brook, Judith S.; Saar, Naomi S.; Zhang, Chenshu; Brook, David W.

    2009-01-01

    Background This study examined the relative impact of familial and non-familial smoking on participant smoking and nicotine dependence. Methods This is a longitudinal study of 838 African American and Puerto Rican participants who were interviewed four times in their homes over a 15–16-year period (1990, 1994–1996, 2000–2001, and 2004–2006). Results Parental smoking during adolescence had a direct positive path to peer smoking during adolescence, which in turn had a direct positive path to participant smoking during the mid-twenties. In addition to the direct path between participant smoking in the mid-twenties and participant nicotine dependence during the late twenties, there was an indirect effect mediated by partner’s problems resulting from smoking during the late twenties. Conclusions This research demonstrates the key role the social environment plays in smoking and nicotine dependence. Both familial and non-familial smoking were significantly related to smoking and nicotine dependence. Public health implications suggest the importance of targeting prevention and treatment policies based on the participants’ stage of development. During adolescence the focus should be on parental and peer smoking, whereas during the twenties attention might be paid to their own smoking and that of their partners. PMID:19101100

  1. Cigarette smoke exposure during adolescence enhances sensitivity to the rewarding effects of nicotine in adulthood, even after a long period of abstinence.

    PubMed

    de la Peña, June Bryan; Ahsan, Hafiz Muhammad; Tampus, Reinholdgher; Botanas, Chrislean Jun; dela Peña, Irene Joy; Kim, Hee Jin; Sohn, Aeree; dela Peña, Ike; Shin, Chan Young; Ryu, Jong Hoon; Cheong, Jae Hoon

    2015-12-01

    Adolescence is a period of enhanced vulnerability to the motivational properties of tobacco/cigarette smoking. Several studies have suggested that smoking initiation during this period will more likely lead to long-lasting cigarette or nicotine addiction. In the present study, we investigated the influences of adolescent cigarette smoke or nicotine exposure on the rewarding effects of nicotine, particularly whether these influences persist even after a long period of abstinence. Towards this, adolescent and adult Sprague-Dawley rats were repeatedly exposed to cigarette smoke or nicotine, for 14 days, and then were subjected to a 1-month abstinence period. Thereafter, the rewarding effects of nicotine were evaluated through the conditioned place preference (CPP) and self-administration (SA) tests. Even after a 1-month abstinence period, rats pre-exposed to either nicotine or cigarette smoke demonstrated enhanced CPP for the higher dose (0.6 mg/kg) of nicotine. Notably, cigarette smoke-preexposed adolescent rats, now adults, showed CPP for both 0.2 and 0.6 mg/kg dose of nicotine. Moreover, only these rats (pre-exposed to cigarette smoke during adolescence) showed significant acquisition and maintenance of nicotine (0.03 mg/kg/infusion) SA. These results suggest that cigarette smoke exposure during adolescence enhances sensitivity to the rewarding effects of nicotine in adulthood, even after a long period of abstinence. This may be a factor in the high rates of nicotine addiction and dependence observed in smokers who started during adolescence. More importantly, our findings highlight the enduring consequences of adolescent-onset cigarette smoking and the need to protect this vulnerable population.

  2. Relationships between trait urgency, smoking reinforcement expectancies, and nicotine dependence.

    PubMed

    Pang, Raina D; Hom, Marianne S; Geary, Bree A; Doran, Neal; Spillane, Nichea S; Guillot, Casey R; Leventhal, Adam M

    2014-01-01

    Urgency (i.e., the tendency to act rashly during negative/positive affect) may increase vulnerability to a variety of risky behaviors. This cross-sectional study of nontreatment-seeking smokers examined the relationship between urgency, level of nicotine dependence, and smoking reinforcement expectancies. Both positive and negative urgency were associated with nicotine dependence. Mediational analyses illustrated that smoking reinforcement expectancies significantly accounted for urgency-dependence relations, with negative reinforcement expectancies displaying incremental mediational effects. If replicated and extended, these findings may support the use of treatments that modify beliefs regarding smoking reinforcement outcomes as a means of buffering the risk of nicotine dependence carried by urgency.

  3. Locomotor response to acute nicotine in adolescent mice is altered by maternal undernutrition during lactation.

    PubMed

    Dutra-Tavares, Ana C; Manhães, Alex C; Silva, Juliana O; Nunes-Freitas, André L; Conceição, Ellen P S; Moura, Egberto G; Lisboa, Patrícia C; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Ribeiro-Carvalho, Anderson

    2015-12-01

    Undernutrition during brain development causes long lasting alterations in different neurotransmitter systems that may alter responses to psychoactive drugs. Despite the recognized effects of early undernutrition on the cholinergic system, no evidence that demonstrates the influence of this insult on nicotine susceptibility has been reported. We investigated the effects of protein/calorie restriction during lactation on the susceptibility to nicotine in adolescent mice. Dams were randomly assigned to one of the following groups: Control (C, 20 litters)--free access to standard laboratory diet (23% protein); Protein Restricted (PR, 12 litters)--free access to a isoenergetic, 8% protein diet; Calorie Restricted (CR, 12 litters)--access to standard laboratory diet in restricted quantities (mean ingestion of PR: pair-fed group). Undernutrition extended from postnatal day 2 (PN2) to weaning (PN21). At PN30, animals either received an i.p. injection of nicotine (0.5mg/Kg) or saline and were immediately placed in open field (OF). After the OF, adrenal glands and serum were collected for the analyses of stress-related endocrine parameters and leptin concentration. PR and CR offspring showed less body mass gain and visceral fat mass. PR offspring presented reduced serum leptin concentration. In the OF, nicotine increased locomotor activity of C and PR, but not of CR. CR and PR offspring showed decreased adrenal catecholamine content, which was not dependent on nicotine exposure. Our results indicate that early undernutrition interferes with nicotine-elicited locomotor effects in adolescent mice and suggest that endocrine parameters alterations in malnourished animals do not influence the behavioral response to nicotine.

  4. Adolescent (Mis)Perceptions about Nicotine Addiction: Results from a Mixed-Methods Study

    ERIC Educational Resources Information Center

    Roditis, Maria; Lee, Joann; Halpern-Felsher, Bonnie L.

    2016-01-01

    Purpose: Despite evidence that adolescents become addicted to nicotine even after limited use, adolescents believe they can experiment with or smoke cigarettes for a few years and easily quit. The goal of this study was to examine adolescents' understanding of the definition and process of nicotine addiction using a mixed-methods approach. Method:…

  5. [New prospects of nicotine dependence treatment--vaccines].

    PubMed

    Goniewicz, Maciej Lukasz; Koszowski, Bartosz; Czogała, Jan; Zymełka, Anna

    2006-01-01

    Smoking is considered to be one of the main threats to health in many societies around the world. Despite carrying out numerous large-scale campaigns promoting a healthy life-style and stimulant avoidance, nicotine dependence still concerns a huge group of people. What is more, almost half of the population is exposed to passive contact with tobacco smoke. At present, there is a whole range of pharmaceutical and non-pharmaceutical means of fighting nicotine dependence. The dramatic development of medical sciences in recent years, especially of the fields connected with biotechnology, resulted in working out of a new method of nicotinism treatment--antinicotinic vaccines. The starting point for working out of such drugs was the mechanism of nicotine action on central nervous system. The idea behind the vaccine is to prevent nicotine from passing through the blood-brain barrier. Nicotine molecules, due to their size and lipophilic character, can easily enter the brain. The mechanism of the antinicotinic vaccine's action consists in producing specific antibodies, which combined with nicotine in the bloodstream are to create immune complexes big enough not to enter the brain. Currently, clinical trails of three vaccines are being carried out: TA-NIC (Xenova Group, UK), NicVAX (NABI Biopharmaceuticals, USA), CYT002-NicQb (Cytos Biotechnology, Switzerland). The results indicate that this form of treatment is interesting when it comes to its effectiveness and in the future may become a routine method of nicotine dependence treatment. PMID:17288232

  6. Genetic Relationship between Schizophrenia and Nicotine Dependence

    PubMed Central

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S.; Kranzler, Henry R.; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Tyndale, Rachel F.; Ware, Jennifer J.; Vink, Jacqueline M.; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning; Ware, Jennifer J.; Chen, Xiangning; Vink, Jacqueline M.; Loukola, Anu; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Mangino, Massimo; Menni, Cristina; Chen, Jingchun; Peterson, Roseann; Auro, Kirsi; Lyytikäinen, Leo-Pekka; Wedenoja, Juho; Stiby, Alex I.; Hemani, Gibran; Willemsen, Gonneke; Hottenga, Jouke Jan; Korhonen, Tellervo; Heliövaara, Markku; Perola, Markus; Rose, Richard; Paternoster, Lavinia; Timpson, Nic; Wassenaar, Catherine A.; Zhu, Andy Z. X.; Smith, George Davey; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Koskinen, Seppo; Spector, Timothy; Penninx, Brenda W. J. H.; Salomaa, Veikko; Boomsma, Dorret I.; Tyndale, Rachel F.; Kaprio, Jaakko; Munafò, Marcus; Ware, Jennifer J.; Chen, Xiangning; Vink, Jacqueline M.; Loukola, Anu; Minica, Camelia; Chen, Jingchun; Peterson, Roseann; Timpson, Nic; Taylor, Michelle; Boomsma, Dorret I.; Kaprio, Jaakko; Munafò, Marcus; Maes, Hermine; Riley, Brien; Kendler, Kenneth S.; Gelernter, Joel; Sherva, Richard; Farrer, Lindsay; Kranzler, Henry R.; Maher, Brion; Vanyukov, Michael

    2016-01-01

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10−3 and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10−3 and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity. PMID:27164557

  7. Genetic Relationship between Schizophrenia and Nicotine Dependence.

    PubMed

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S; Kranzler, Henry R; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I; Penninx, Brenda W J H; Tyndale, Rachel F; Ware, Jennifer J; Vink, Jacqueline M; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning

    2016-01-01

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity. PMID:27164557

  8. Genetic Relationship between Schizophrenia and Nicotine Dependence.

    PubMed

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S; Kranzler, Henry R; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I; Penninx, Brenda W J H; Tyndale, Rachel F; Ware, Jennifer J; Vink, Jacqueline M; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning

    2016-05-10

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.

  9. Associations between nicotine dependence, anhedonia, urgency and smoking motives.

    PubMed

    Roys, Melanie; Weed, Keri; Carrigan, Maureen; MacKillop, James

    2016-11-01

    Models of nicotine dependence have suggested that the association between urgency, a subconstruct of impulsivity, and smoking behaviors may be mediated by motivations. Motives that are driven by expectations that smoking will relieve negative affect or increase positive affect may be especially salient in persons who have depression symptoms such as anhedonia. Support for associations between symptoms of depression, urgency, and addiction has been found for alcohol dependence, but empirical analysis is lacking for an interactive effect of urgency and depression symptoms on nicotine dependence. The current study investigated relationships among the urgency facet of impulsivity, anhedonia, smoking motives, and nicotine dependence with secondary analyses of a sample of 1084 daily smokers using simultaneous moderation and multiple mediation analyses. The moderation analysis revealed that although urgency was significantly associated with smoking at average or higher levels of anhedonia, it was unrelated to smoking when few anhedonia symptoms were endorsed. Further, multiple mediation analyses revealed that the smoking motives of craving, cue exposure, positive reinforcement, and tolerance significantly mediated the relationship between urgency and nicotine dependence. Results suggest that models of alcohol addiction that include an interactive effect of urgency and certain symptoms of depression may be applied to nicotine dependence. Examination of the multiple mediational pathways between urgency and nicotine dependence suggests directions for intervention efforts. PMID:27376882

  10. Administration of nicotine to adolescent rats evokes regionally selective upregulation of CNS alpha 7 nicotinic acetylcholine receptors.

    PubMed

    Slotkin, Theodore A; Cousins, Mandy M; Seidler, Frederic J

    2004-12-24

    Alpha 7 Nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore targets for developmental neurotoxicants. We administered nicotine to adolescent rats and evaluated the effects on alpha 7 nAChRs in the striatum, brainstem and cerebellum. During the period of nicotine administration (30-47.5 days of age), nicotine elicited alpha 7 nAChR upregulation with a regional hierarchy of striatum>brainstem>cerebellum. Values returned to normal or became slightly subnormal almost immediately after the cessation of treatment (50 days of age) with no further changes through 75 days of age. The temporal and regional patterns of the effects on alpha 7 nAChRs were distinct from those reported earlier for the alpha 4 beta 2 subtype, and neither adult nor fetal/neonatal administration upregulates the alpha 7 subtype in the striatum. Targeting of the striatum is thus unique to nicotine exposure during adolescence and parallels earlier work showing regionally selective effects of this treatment on synaptic signaling. We obtained preliminary evidence for nicotine-induced oxidative stress as a potential contributory mechanism. The present findings reinforce the concept of biologically distinct effects of nicotine in the adolescent brain and provide evidence for a mechanistic involvement of alpha 7 nAChRs in its unique effects during this developmental period.

  11. Transgenerational effects of adolescent nicotine exposure in rats: Evidence for cognitive deficits in adult female offspring.

    PubMed

    Renaud, Samantha M; Fountain, Stephen B

    2016-01-01

    This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4days of massed training (20patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a "violation element" of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation.

  12. Development of the PROMIS® Nicotine Dependence Item Banks

    PubMed Central

    Edelen, Maria Orlando; Tucker, Joan S.; Stucky, Brian D.; Hansen, Mark; Cai, Li

    2014-01-01

    Introduction: Nicotine dependence is a core construct important for understanding cigarette smoking and smoking cessation behavior. This article describes analyses conducted to develop and evaluate item banks for assessing nicotine dependence among daily and nondaily smokers. Methods: Using data from a sample of daily (N = 4,201) and nondaily (N =1,183) smokers, we conducted a series of item factor analyses, item response theory analyses, and differential item functioning analyses (according to gender, age, and race/ethnicity) to arrive at a unidimensional set of nicotine dependence items for daily and nondaily smokers. We also evaluated performance of short forms (SFs) and computer adaptive tests (CATs) to efficiently assess dependence. Results: A total of 32 items were included in the Nicotine Dependence item banks; 22 items are common across daily and nondaily smokers, 5 are unique to daily smokers, and 5 are unique to nondaily smokers. For both daily and nondaily smokers, the Nicotine Dependence item banks are strongly unidimensional, highly reliable (reliability = 0.97 and 0.97, respectively), and perform similarly across gender, age, and race/ethnicity groups. SFs common to daily and nondaily smokers consist of 8 and 4 items (reliability = 0.91 and 0.81, respectively). Results from simulated CATs showed that dependence can be assessed with very good precision for most respondents using fewer than 6 items adaptively selected from the item banks. Conclusions: Nicotine dependence on cigarettes can be assessed on the basis of these item banks via one of the SFs, by using CATs, or through a tailored set of items selected for a specific research purpose. PMID:25118226

  13. Exploring brief measures of nicotine dependence for epidemiological surveys.

    PubMed

    de Leon, Jose; Diaz, Francisco J; Becoña, Elisardo; Gurpegui, Manuel; Jurado, Dolores; Gonzalez-Pinto, Ana

    2003-10-01

    A score > or = 6 in the Fagerström Test for Nicotine Dependence (FTND), identifying high nicotine dependence, was compared with three briefer classifications: (1) Item 4: heavy smoking (more than 30 cigarettes per day); (2) Item 1: high early smoking (smoking within 30 min of waking up); and (3) a score > or = 4 by combining Items 1 and 4. The FTND scores from 1642 smokers from five samples in the US and Spain were analyzed. Heavy smoking had low sensitivity. High early smoking had low specificity. A score > or = 4 by combining Items 1 and 4 had relatively good sensitivity (94%) and specificity (88%). Researchers needing definition of nicotine dependence briefer than FTND may want to only use Items 1 and 4 of FTND with a cutting score > or = 4. PMID:14512071

  14. A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels.

    PubMed

    Feng, Zhaoyang; Li, Wei; Ward, Alex; Piggott, Beverly J; Larkspur, Erin R; Sternberg, Paul W; Xu, X Z Shawn

    2006-11-01

    Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses.

  15. Low-dose adolescent nicotine and methylphenidate have additive effects on adult behavior and neurochemistry.

    PubMed

    Wheeler, Tracey L; Smith, Laura N; Bachus, Susan E; McDonald, Craig G; Fryxell, Karl J; Smith, Robert F

    2013-02-01

    Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) have higher rates of smoking than adolescents without ADHD. Since methylphenidate is the primary drug used to treat ADHD, it is likely that many adolescents are exposed to both methylphenidate and nicotine. Recent studies have established that adolescent nicotine induces long-term changes in several neurobehavioral variables. Limited data also suggest that adolescent methylphenidate may affect neural development. Nicotine tolerance is a well-established behavioral phenomenon in rodents, yet the underlying mechanism remains elusive. Recent theories suggest that changes in ventral striatal dopamine indices may relate to nicotine tolerance. As an initial determination of whether nicotine and methylphenidate have additive effects on neurobehavioral development, the present study investigated the combined effects of adolescent nicotine [2mg/kg/d] alone or in conjunction with methylphenidate [1.5mg/kg, 2× daily] following a one-month drug free period on adult behavioral tolerance to nicotine [0.5mg/kg s.c.] and its relation to dopamine receptor mRNA expression in the ventral striatum. Animals with chronic combined (nicotine+methylphenidate) adolescent exposure displayed stronger tolerance as adults to the nicotine-induced locomotor effects in comparison to animals with adolescent exposure to nicotine alone, methylphenidate alone, or controls. Combined chronic adolescent exposure significantly elevated adult D3nf mRNA expression levels in the nucleus accumbens, however a single nicotine injection in adults increased D3nf mRNA levels in naïve animals and decreased D3nf mRNA levels in those that had been previously exposed to combined stimulants during adolescence. Conversely, a single adult nicotine injection increased D1 mRNA levels in the adult nucleus accumbens, particularly in the shell, but only in rats previously exposed to nicotine or methylphenidate as adolescents. To our knowledge this is the first

  16. Cadmium increases the sensitivity of adolescent female mice to nicotine-related behavioral deficits.

    PubMed

    Adeniyi, Philip Adeyemi; Olatunji, Babawale Peter; Ishola, Azeez Olakunle; Ajonijebu, Duyilemi Chris; Ogundele, Olalekan Michael

    2014-01-01

    This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain) were divided into four groups of five (n = 5) mice each. A set of mice (Nic) received subcutaneous nicotine (2.0 mg/kg) while a separate set (Cd) was treated with 2.0 mg/kg cadmium (subcutaneous). For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n = 5; control) received normal saline. The total duration of treatment for all groups was 28 days (P28-P56). At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory.

  17. Validity of a Demand Curve Measure of Nicotine Reinforcement with Adolescent Smokers

    PubMed Central

    Murphy, James G.; MacKillop, James; Tidey, Jennifer W.; Brazil, Linda A.; Colby, Suzanne M.

    2010-01-01

    High or inelastic demand for drugs is central to many laboratory and theoretical models of drug abuse, but it has not been widely measured with human substance abusers. The authors used a simulated cigarette purchase task to generate a demand curve measure of nicotine reinforcement in a sample of 138 adolescent smokers. Participants reported the number of cigarettes they would purchase and smoke in a hypothetical day across a range of prices, and their responses were well-described by a regression equation that has been used to construct demand curves in drug self-administration studies. Several demand curve measures were generated, including breakpoint, intensity, elasticity, Pmax, and Omax. Although simulated cigarette smoking was price sensitive, smoking levels were high (8+ cigarettes/day) at prices up to 50¢ per cigarette, and the majority of the sample reported that they would purchase at least 1 cigarette at prices as high as $2.50 per cigarette. Higher scores on the demand indices Omax (maximum cigarette purchase expenditure), intensity (reported smoking level when cigarettes were free), and breakpoint (the first price to completely suppress consumption), and lower elasticity (sensitivity of cigarette consumption to increases in cost), were associated with greater levels of naturalistic smoking and nicotine dependence. Greater demand intensity was associated with lower motivation to change smoking. These results provide initial support for the validity of a self-report cigarette purchase task as a measure of economic demand for nicotine with adolescent smokers. PMID:20832200

  18. Addressing Nicotine Dependence in Psychodynamic Psychotherapy: Perspectives from Residency Training

    ERIC Educational Resources Information Center

    Prochaska, Judith J.; Fromont, Sebastien C.; Banys, Peter; Eisendrath, Stuart J.; Horowitz, Mardi J.; Jacobs, Marc H.; Hall, Sharon M.

    2007-01-01

    Objective: According to APA treatment recommendations, psychiatrists should assess and intervene in tobacco use with all of their patients who smoke. The ease with which this occurs may vary by treatment model. This study examined perspectives in residency training to identify a framework for addressing nicotine dependence within psychodynamic…

  19. CYP2A6 Polymorphisms May Strengthen Individualized Treatment for Nicotine Dependence

    PubMed Central

    Akrodou, Yawo Mawuli

    2015-01-01

    Each CYP2A6 gene variant metabolizes nicotine differently depending on its enzymatic activities. The normal nicotine metabolizer CYP2A6*1A is associated with high scores of nicotine dependence (5–10) on the Fagerström Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Slow nicotine metabolizers (i.e., CYP2A6*1H, CYP2A6*4A, CYP2A6*9, and CYP2A6*12A) are associated with underrated nicotine metabolizing activity (50%–75%), linking them to low scores for nicotine dependence (0–4) on the FTND scale. In a clinical trial involving the use of bupropion, people who were carriers of slow nicotine metabolizers were found to have a tendency to maintain abstinence 1.7 times longer than people with normal nicotine metabolizers. An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence. PMID:26060595

  20. Relationship of Nicotine Dependence, Subsyndromal and Pathological Gambling, and Other Psychiatric Disorders

    PubMed Central

    Grant, Jon E.; Desai, Rani A.; Potenza, Marc N.

    2013-01-01

    Objective Nicotine dependence frequently co-occurs with subsyndromal and pathological levels of gambling. The relationship of nicotine dependence, levels of gambling pathology, and other psychiatric disorders, however, is incompletely understood. Method To use nationally representative data to examine the influence of DSM-IV nicotine dependence on the association between pathological gambling severities and other psychiatric disorders. Face-to-face interviews were conducted in 43,093 household and group-quarters adults in the United States. The main outcome measure was the co-occurrence of current nicotine dependence and Axis I and II disorders and severity of gambling based on the ten inclusionary diagnostic criteria for pathological gambling. Results Among non-nicotine-dependent respondents, increasing gambling severity was associated with greater psychopathology for the majority of Axis I and II disorders. This pattern was not uniformly observed among nicotine dependent subjects. Significant nicotine-by-gambling-group interactions were observed for multiple Axis I and II disorders. All significant interactions involved stronger associations between gambling and psychopathology in the non-nicotine-dependent group. Conclusions In a large national sample, nicotine dependence influences the associations between gambling and multiple psychiatric disorders. Subsyndromal levels of gambling are associated with significant psychopathology. Nicotine dependence accounts for some of the elevated risks for psychopathology associated with subsyndromal and problem/pathological levels of gambling. Additional research is needed to examine specific prevention and treatment for individuals with problem/pathological gambling with and without nicotine dependence. PMID:19254518

  1. Nicotinic receptor modulation to treat alcohol and drug dependence

    PubMed Central

    Rahman, Shafiqur; Engleman, Eric A.; Bell, Richard L.

    2015-01-01

    Alcohol and drug dependence are serious public health problems worldwide. The prevalence of alcohol and drug dependence in the United States and other parts of the world is significant. Given the limitations in the efficacy of current pharmacotherapies to treat these disorders, research in developing alternative pharmacotherapies continues. Preclinical and clinical evidence thus far has indicated that brain nicotinic acetylcholine receptors (nAChRs) are important pharmacological targets for the development of medications to treat alcohol and drug dependence. The nAChRs are a super family of ligand gated ion channels, and are expressed throughout the brain with twelve neuronal nAChR subunits (α2–α10 and β2–β4) identified. Here, we review preclinical and clinical evidence involving a number of nAChR ligands that target different nAChR subtypes in alcohol and nicotine addiction. The important ligands include cytisine, lobeline, mecamylamine, varenicline, sazetidine A and others that target α4β2* nAChR subtypes as small molecule modulators of the brain nicotinic cholinergic system are also discussed. Taken together, both preclinical and clinical data exist that support nAChR–based ligands as promising therapeutic agents for the treatment of alcohol and drug dependence. PMID:25642160

  2. A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence

    PubMed Central

    Grucza, Richard A; Wang, Jen C.; Stitzel, Jerry A.; Hinrichs, Anthony L.; Saccone, Scott F.; Saccone, Nancy L.; Bucholz, Kathleen K.; Cloninger, C. Robert; Neuman, Rosalind J.; Budde, John P.; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John. I.; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A.; Edenberg, Howard J.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2008-01-01

    Background A non-synonymous coding polymorphism, rs16969968, of the CHRNA5 gene which encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence (20). The goal of the present study is to examine the association of this variant with cocaine dependence. Methods Genetic association analysis in two, independent samples of unrelated cases and controls; 1.) 504 European-American participating in the Family Study on Cocaine Dependence (FSCD); 2.) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholsim (COGA). Results In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (OR = 0.67 per allele, p = 0.0045, assuming an additive genetic model), but in the reverse direction compared to that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. Conclusion The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways. PMID:18519132

  3. Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.

    PubMed

    Locker, Alicia R; Marks, Michael J; Kamens, Helen M; Klein, Laura Cousino

    2016-05-01

    Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway during adolescence through drug use may produce neural alterations affecting subsequent drug consumption. Consequently, the effect of nicotine exposure on binge alcohol consumption was examined along with an assessment of the neurobiological underpinnings that drive adolescent use of these drugs. Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or nicotine (200μg/ml) for ten days. On the final four days, ethanol intake was examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed significantly more ethanol and displayed higher blood ethanol concentrations than did control mice. Autoradiographic analysis of nAChR density revealed higher epibatidine binding in frontal cortical regions in mice exposed to nicotine and ethanol compared to mice exposed to ethanol only. These data show that nicotine exposure during adolescence increases subsequent binge ethanol consumption, and may affect the number of nAChRs in regions of the brain reward pathway, specifically the frontal cortex.

  4. The genetics of nicotine dependence: relationship to pancreatic cancer.

    PubMed

    MacLeod, Stewart L; Chowdhury, Parimal

    2006-12-14

    Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled case-control studies to identify target genes and deduce mechanisms that account for the genetic basis of inter-individual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.

  5. Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine.

    PubMed

    Slotkin, Theodore A; Stadler, Ashley; Skavicus, Samantha; Seidler, Frederic J

    2016-04-01

    Cardiovascular responses to smoking cessation may differ in adolescents compared to adults. We administered nicotine by osmotic minipump infusion for 17 days to adolescent and adult rats (30 and 90 days of age, respectively) and examined cardiac norepinephrine levels during treatment, after withdrawal, and for months after cessation. In adults, nicotine evoked a significant elevation of cardiac norepinephrine and a distinct spike upon withdrawal, after which the levels returned to normal; the effect was specific to males. In contrast, adolescents did not show significant changes during nicotine treatment or in the immediate post-withdrawal period. However, beginning in young adulthood, males exposed to adolescent nicotine showed sustained elevations of cardiac norepinephrine, followed by later-emerging deficits that persisted through six months of age. We then conducted adolescent exposure using twice-daily injections, a regimen that augments stress associated with inter-dose withdrawal episodes. With the injection route, adolescents showed an enhanced cardiac norepinephrine response, reinforcing the relationship between withdrawal stress and a surge in cardiac norepinephrine levels. The relative resistance of adolescents to the acute nicotine withdrawal response is likely to make episodic nicotine exposure less stressful or aversive than in adults. Equally important, the long-term changes after adolescent nicotine exposure resemble those known to be associated with risk of hypertension in young adulthood (elevated norepinephrine) or subsequent congestive heart disease (norepinephrine deficits). Our findings reinforce the unique responses and consequences of nicotine exposure in adolescence, the period in which most smokers commence tobacco use. PMID:26993795

  6. Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine.

    PubMed

    Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M; DeSimone, John A; Lyall, Vijay

    2015-01-01

    Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol.

  7. A signal peptide missense mutation associated with nicotine dependence alters α2*-nicotinic acetylcholine receptor function.

    PubMed

    Dash, Bhagirathi; Lukas, Ronald J; Li, Ming D

    2014-04-01

    A cytosine to thymidine (C → T) missense mutation in the signal peptide (SP) sequence (rs2472553) of the nicotinic acetylcholine receptor (nAChR) α2 subunit produces a threonine-to-isoleucine substitution (T22I) often associated with nicotine dependence (ND). We assessed effects on function of α2*-nAChR ('*'indicates presence of additional subunits) of this mutation, which could alter SP cleavage, RNA/protein secondary structure, and/or efficiency of transcription, translation, subunit assembly, receptor trafficking or cell surface expression. Two-electrode voltage clamp analyses indicate peak current responses to ACh or nicotine are decreased 2.8-5.8-fold for putative low sensitivity (LS; 10:1 ratio of α:β subunit cRNAs injected) α2β2- or α2β4-nAChR and increased for putative high sensitivity (HS; 1:10 α:β subunit ratio) α2β2- (5.7-15-fold) or α2β4- (1.9-2.2-fold) nAChR as a result of the mutation. Agonist potencies are decreased 1.6-4-fold for putative LS or HS α2(T22I)β2-nAChR or for either α2*-nAChR subtype formed in the presence of equal amounts of subunit cRNA, slightly decreased for LS α2(T22I)β4-nAChR, but increased 1.4-2.4-fold for HS α2(T22I)β4-nAChR relative to receptors containing wild-type α2 subunits. These effects suggest that the α2 subunit SP mutation generally favors formation of LS receptor isoforms. We hypothesize that lower sensitivity of human α2*-nAChR to nicotine could contribute to increased susceptibility to ND. To our knowledge this is the first report of a SP mutation having a functional effect in a member of cys-loop family of ligand-gated ion channels.

  8. Thyroid receptor β involvement in the effects of acute nicotine on hippocampus-dependent memory.

    PubMed

    Leach, Prescott T; Kenney, Justin W; Connor, David A; Gould, Thomas J

    2015-06-01

    Cigarette smoking is common despite adverse health effects. Nicotine's effects on learning may contribute to addiction by enhancing drug-context associations. Effects of nicotine on learning could be direct or could occur by altering systems that modulate cognition. Because thyroid signaling can alter cognition and nicotine/smoking may change thyroid function, nicotine could affect learning through changes in thyroid signaling. These studies investigate the functional contributions of thyroid receptor (TR) subtypes β and α1 to nicotine-enhanced learning and characterize the effects of acute nicotine and learning on thyroid hormone levels. We conducted a high throughput screen of transcription factor activity to identify novel targets that may contribute to the effects of nicotine on learning. Based on these results, which showed that combined nicotine and learning uniquely acted to increase TR activation, we identified TRs as potential targets of nicotine. Further analyses were conducted to determine the individual and combined effects of nicotine and learning on thyroid hormone levels, but no changes were seen. Next, to determine the role of TRβ and TRα1 in the effects of nicotine on learning, mice lacking the TRβ or TRα1 gene and wildtype littermates were administered acute nicotine prior to fear conditioning. Nicotine enhanced contextual fear conditioning in TRα1 knockout mice and wildtypes from both lines but TRβ knockout mice did not show nicotine-enhanced learning. This finding supports involvement of TRβ signaling in the effect of acute nicotine on hippocampus-dependent memory. Acute nicotine enhances learning and these effects may involve processes regulated by the transcription factor TRβ. PMID:25666034

  9. Measures and models of nicotine dependence: positive reinforcement.

    PubMed

    Glautier, Steven

    2004-06-01

    This paper addresses the problem of assessing nicotine dependence. The main objective is to develop theory-led suggestions for measures that will be relevant in the early phases of tobacco use, as well as in established smokers. Theoretical models of addiction falling into the general class of 'positive reinforcement theories' were identified and reviewed. From this review a number of drug effects and patterns of behaviour were distilled and categorized as either vulnerability or dependence indicators. A comparison of those features with the International Classification of Diseases (ICD-10) and Diagnostic and Statistical Manual (DSM-IV) diagnostic systems shows that neither system includes detailed assessment of vulnerability indicators. It is argued that measurement of vulnerability indicators, in addition to dependence indicators, may add to the predictive validity of assessments carried out in early career tobacco users, especially where there is limited evidence of established dependence. In addition, it is suggested that examination of measures that differentiate a subgroup of early career smokers termed 'rapid accelerators' may prove profitable and enable identification of the key parameters of nicotine reinforcement.

  10. Spanish adaptation of the NDSS (Nicotine Dependence Syndrome Scale) and assessment of nicotine-dependent individuals at primary care health centers in Spain.

    PubMed

    Becoña, Elisardo; López, Ana; Fernández del Río, Elena; Míguez, Ma Carmen; Castro, Josefina

    2010-11-01

    The availability of adequate instruments for the assessment of nicotine dependence is an important factor that is relevant in the area of tobacco addiction. In this study, we present a Spanish validation of the Nicotine Dependence Syndrome Scale (NDSS) (Shiffman, Waters, & Hickcox, 2004). The sample was composed ofpatients, all daily smokers, who visited their General Practitioner (GP) at five Primary Health Care Centers in different cities of Spain (N = 637). The results indicated adequate reliability for the general factor that assesses nicotine dependence (NDSS-Total) (Cronbach's alpha = .76). Factor analysis confirms the five factors of the original validation: Drive, Continuity, Stereotypy, Priority, and Tolerance. It must be noted that reliability is adequate for the first, and moderate or low for the rest. The NDSS-T and its scales correlate significantly with the Fagerström Test for Nicotine Dependence (FTND), with the nicotine dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) as assessed through the Structured Clinical Interview for DSM-IV (SCID), with carbon monoxide levels in expired air (CO), and with the number of cigarettes smoked. The ROC curve indicates that the NDSS-T has a score of .79 which is under the curve (.69 for the FTND), thus the prediction of nicotine dependence is adequate. We conclude that this instrument is useful (in terms of its total score NDSS-T) for assessing nicotine dependence for Spanish smokers (in Spain), as has been found in other countries, language groups, and cultures.

  11. Adolescent vulnerabilities to chronic alcohol or nicotine exposure: findings from rodent models.

    PubMed

    Barron, Susan; White, Aaron; Swartzwelder, H Scott; Bell, Richard L; Rodd, Zachary A; Slawecki, Craig J; Ehlers, Cindy L; Levin, Edward D; Rezvani, Amir H; Spear, Linda P

    2005-09-01

    This article presents an overview of the proceedings from a symposium entitled "Is adolescence special? Possible age-related vulnerabilities to chronic alcohol or nicotine exposure," organized by Susan Barron and Linda Spear and held at the 2004 Research Society on Alcoholism Meeting in Vancouver, British Columbia. This symposium, co-sponsored by the Fetal Alcohol Syndrome Study Group and the Neurobehavioral Teratology Society, focused on our current knowledge regarding the long-term consequences of ethanol and/or nicotine exposure during adolescence with the emphasis on data from rodent models. The support from these two societies represents the understanding by these research groups that adolescence represents a unique developmental stage for the effects of chronic drug exposure and also marks an age in which many risky behaviors including alcohol consumption and smoking typically begin. The speakers included (1) Aaron White, who presented data on the effects of adolescent ethanol exposure on subsequent motor or cognitive response to an ethanol challenge in adulthood; (2) Richard Bell, who presented data suggesting that genetic differences could play a role in adolescent vulnerability to ethanol; (3) Craig Slawecki, who presented data looking at the effects of chronic exposure to alcohol or nicotine on neurophysiologic and behavioral end points; and (4) Ed Levin, who presented data on acute and long-term consequences of adolescent nicotine exposure. Finally, Linda Spear provided some summary points and recommendations regarding unresolved issues and future directions.

  12. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    PubMed Central

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  13. Candidate genes for nicotine dependence via linkage, epistasis, and bioinformatics.

    PubMed

    Sullivan, Patrick F; Neale, Benjamin M; van den Oord, Edwin; Miles, Michael F; Neale, Michael C; Bulik, Cynthia M; Joyce, Peter R; Straub, Richard E; Kendler, Kenneth S

    2004-04-01

    Many smoking-related phenotypes are substantially heritable. One genome scan of nicotine dependence (ND) has been published and several others are in progress and should be completed in the next 5 years. The goal of this hypothesis-generating study was two-fold. First, we present further analyses of our genome scan data for ND published by Straub et al. [1999: Mol Psychiatry 4:129-144] (PMID: 10208445). Second, we used the method described by Cox et al. [1999: Nat Genet 21:213-215] (PMID: 9988276) to search for epistatic loci across the markers used in the genome scan. The overall results of the genome scan nearly reached the rigorous Lander and Kruglyak [1995: Nat Genet 11:241-247] criteria for "significant" linkage with the best findings on chromosomes 10 and 2. We then looked for correspondence between genes located in the 10 regions implicated in affected sibling pair (ASP) and epistatic linkage analyses with a list of genes suggested by microarray studies of experimental nicotine exposure and candidate genes from the literature. We found correspondence between linkage and microarray/candidate gene studies for genes involved with the mitogen-activated protein kinase (MAPK) signaling system, nuclear factor kappa B (NFKB) complex, neuropeptide Y (NPY) neurotransmission, a nicotinic receptor subunit (CHRNA2), the vesicular monoamine transporter (SLC18A2), genes in pathways implicated in human anxiety (HTR7, TDO2, and the endozepine-related protein precursor, DKFZP434A2417), and the micro 1-opioid receptor (OPRM1). Although the hypotheses resulting from these linkage and bioinformatic analyses are plausible and intriguing, their ultimate worth depends on replication in additional linkage samples and in future experimental studies. PMID:15048644

  14. Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay.

    PubMed

    Locklear, Laura L; McDonald, Craig G; Smith, Robert F; Fryxell, Karl J

    2012-09-01

    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.

  15. Thyroid Receptor β Involvement in the Effects of Acute Nicotine on Hippocampus-Dependent Memory

    PubMed Central

    Leach, Prescott T.; Kenney, Justin W.; Connor, David; Gould, Thomas J.

    2015-01-01

    Cigarette smoking is common despite adverse health effects. Nicotine’s effects on learning may contribute to addiction by enhancing drug-context associations. Effects of nicotine on learning could be direct or could occur by altering systems that modulate cognition. Because thyroid signaling can alter cognition and nicotine/smoking may change thyroid function, nicotine could affect learning through changes in thyroid signaling. These studies investigate the functional contributions of thyroid receptor (TR) subtypes β and α1 to nicotine-enhanced learning and characterize the effects of acute nicotine and learning on thyroid hormone levels. We conducted a high throughput screen of transcription factor activity to identify novel targets that may contribute to the effects of nicotine on learning. Based on these results, which showed that combined nicotine and learning uniquely acted to increase TR activation, we identified TRs as potential targets of nicotine. Further analyses were conducted to determine the individual and combined effects of nicotine and learning on thyroid hormone levels, but no changes were seen. Next, to determine the role of TRβ and TRα1 in the effects of nicotine on learning, mice lacking the TRβ or TRα1 gene and wildtype littermates were administered acute nicotine prior to fear conditioning. Nicotine enhanced contextual fear conditioning in TRα1 knockout mice and wildtypes from both lines but TRβ knockout mice did not show nicotine-enhanced learning. This finding supports involvement of TRβ signaling in the effect of acute nicotine on hippocampus-dependent memory. Acute nicotine enhances learning and these effects may involve processes regulated by the transcription factor TRβ. PMID:25666034

  16. Cohort Profile: The Nicotine Dependence in Teens (NDIT) Study.

    PubMed

    O'Loughlin, Jennifer; Dugas, Erika N; Brunet, Jennifer; DiFranza, Joseph; Engert, James C; Gervais, Andre; Gray-Donald, Katherine; Karp, Igor; Low, Nancy C; Sabiston, Catherine; Sylvestre, Marie-Pierre; Tyndale, Rachel F; Auger, Nathalie; Auger, Nathalie; Mathieu, Belanger; Tracie, Barnett; Chaiton, Michael; Chenoweth, Meghan J; Constantin, Evelyn; Contreras, Gisèle; Kakinami, Lisa; Labbe, Aurelie; Maximova, Katerina; McMillan, Elizabeth; O'Loughlin, Erin K; Pabayo, Roman; Roy-Gagnon, Marie-Hélène; Tremblay, Michèle; Wellman, Robert J; Hulst, Andraeavan; Paradis, Gilles

    2015-10-01

    The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999-2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999-2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007-08 and 2011-12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor (www.nditstudy.ca). PMID:25022274

  17. Cohort Profile: The Nicotine Dependence in Teens (NDIT) Study

    PubMed Central

    O’Loughlin, Jennifer; Dugas, Erika N; Brunet, Jennifer; DiFranza, Joseph; Engert, James C; Gervais, Andre; Gray-Donald, Katherine; Karp, Igor; Low, Nancy C; Sabiston, Catherine; Sylvestre, Marie-Pierre; Tyndale, Rachel F; Auger, Nathalie; Barnett, Tracie; Mathieu, Bélanger; Chaiton, Michael; Chenoweth, Meghan J; Constantin, Evelyn; Contreras, Gisèle; Kakinami, Lisa; Labbe, Aurélie; Maximova, Katerina; McMillan, Elizabeth; O’Loughlin, Erin K; Pabayo, Roman; Roy-Gagnon, Marie-Hélène; Tremblay, Michèle; Wellman, Robert J; van Hulst, Andraea; Paradis, Gilles

    2015-01-01

    The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999–2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999–2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007–08 and 2011–12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor (www.nditstudy.ca). PMID:25022274

  18. Cohort Profile: The Nicotine Dependence in Teens (NDIT) Study.

    PubMed

    O'Loughlin, Jennifer; Dugas, Erika N; Brunet, Jennifer; DiFranza, Joseph; Engert, James C; Gervais, Andre; Gray-Donald, Katherine; Karp, Igor; Low, Nancy C; Sabiston, Catherine; Sylvestre, Marie-Pierre; Tyndale, Rachel F; Auger, Nathalie; Auger, Nathalie; Mathieu, Belanger; Tracie, Barnett; Chaiton, Michael; Chenoweth, Meghan J; Constantin, Evelyn; Contreras, Gisèle; Kakinami, Lisa; Labbe, Aurelie; Maximova, Katerina; McMillan, Elizabeth; O'Loughlin, Erin K; Pabayo, Roman; Roy-Gagnon, Marie-Hélène; Tremblay, Michèle; Wellman, Robert J; Hulst, Andraeavan; Paradis, Gilles

    2015-10-01

    The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999-2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999-2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007-08 and 2011-12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor (www.nditstudy.ca).

  19. Impairment of nitric oxide synthase-dependent dilatation of cerebral arterioles during infusion of nicotine.

    PubMed

    Fang, Qin; Sun, Hong; Mayhan, William G

    2003-02-01

    The effects of nicotine on nitric oxide synthase (NOS)-dependent reactivity of cerebral arterioles remain uncertain. Our first goal was to examine whether infusion of nicotine alters NOS-dependent reactivity of cerebral arterioles. Our second goal was to examine the mechanisms that may account for the effects of nicotine on cerebral arterioles. We measured the diameter of pial arterioles to NOS-dependent (ADP and acetylcholine) and NOS-independent (nitroglycerin) agonists before and after the infusion of nicotine (2 microg x kg(-1) x min(-1) iv for 30 min, followed by a maintenance dose of 0.35 microg x kg(-1) x min(-1)). ADP- and acetylcholine-induced vasodilatation was impaired after the infusion of nicotine. In contrast, nicotine did not alter vasodilatation to nitroglycerin. Next, we examined whether the impaired responses of pial arterioles during infusion of nicotine may be related to oxygen radicals. We found that application of superoxide dismutase or tetrahydrobiopterin during infusion of nicotine could prevent impaired NOS-dependent vasodilatation. Thus acute exposure of cerebral vessels to nicotine specifically impairs NOS-dependent dilatation via the production of oxygen radicals possibly related to an alteration in the utilization of tetrahydrobiopterin.

  20. Associations of mindfulness with nicotine dependence, withdrawal, and agency.

    PubMed

    Vidrine, Jennifer Irvin; Businelle, Michael S; Cinciripini, Paul; Li, Yisheng; Marcus, Marianne T; Waters, Andrew J; Reitzel, Lorraine R; Wetter, David W

    2009-01-01

    Quitting smoking is a major life stressor that results in numerous aversive consequences, including persistently increased level of post-cessation negative affect and relapse. The identification of factors that may enhance behavioral and emotional regulation after quitting may be useful in enhancing quit rates and preventing relapse. One factor broadly linked with behavioral and emotional regulation is mindfulness. This study examined baseline associations of mindfulness with demographic variables, smoking history, dependence, withdrawal severity, and agency among 158 smokers enrolled in a cessation trial. Results indicated that mindfulness was negatively associated with level of nicotine dependence and withdrawal severity, and positively associated with a sense of agency regarding cessation. Moreover, mindfulness remained significantly associated with these measures even after controlling for key demographic variables. Results suggest that low level of mindfulness may be an important predictor of vulnerability to relapse among adult smokers preparing to quit; thus, mindfulness-based interventions may enhance cessation.

  1. Associations of Mindfulness with Nicotine Dependence, Withdrawal, and Agency

    PubMed Central

    Vidrine, Jennifer Irvin; Businelle, Michael S.; Cinciripini, Paul; Li, Yisheng; Marcus, Marianne T.; Waters, Andrew J.; Reitzel, Lorraine R.; Wetter, David W.

    2016-01-01

    Quitting smoking is a major life stressor that results in numerous aversive consequences, including persistently increased level of post-cessation negative affect and relapse. The identification of factors that may enhance behavioral and emotional regulation after quitting may be useful in enhancing quit rates and preventing relapse. One factor broadly linked with behavioral and emotional regulation is mindfulness. This study examined baseline associations of mindfulness with demographic variables, smoking history, dependence, withdrawal severity, and agency among 158 smokers enrolled in a cessation trial. Results indicated that mindfulness was negatively associated with level of nicotine dependence and withdrawal severity, and positively associated with a sense of agency regarding cessation. Moreover, mindfulness remained significantly associated with these measures even after controlling for key demographic variables. Results suggest that low level of mindfulness may be an important predictor of vulnerability to relapse among adult smokers preparing to quit; thus, mindfulness-based interventions may enhance cessation. PMID:19904667

  2. Tailoring nicotine addiction treatments for chemical dependency patients.

    PubMed

    Orleans, C T; Hutchinson, D

    1993-01-01

    The growing scientific evidence for addressing nicotine addiction in chemical dependency (CD) treatment programs is reviewed. This evidence provided the impetus for a survey of smoking patterns and quitting motivation and barriers among CD patients to identify ways to tailor standard nicotine addiction treatment methods and goals to their needs. Smoking history questionnaires were administered to 118 consecutive patients in a residential CD treatment program. The 66% of patients who smoked were predominantly heavy smokers, highly addicted (mean 25 cigarettes per day, 76% smoking within 30 minutes of waking). Although 63% of patients were "precontemplators," most of the sample had a history of one or more serious quit attempts, most reported strong beliefs in smoking harms and quitting benefits, and almost half reported a strong desire to stop smoking. Major quitting barriers included the usual psychological and physical sequelae of tobacco abstinence in addition to being around other smokers. Surprisingly, very few patients expressed concerns that quitting smoking would threaten drug or alcohol sobriety. Treatment implications are discussed. In addition, a pilot 4-session group treatment program is described. This program was geared to motivating smokers in "precontemplation" and "contemplation" stages of change to move ahead into the "action" stage (i.e., taking steps to quit). PMID:8389897

  3. Superoxide dismutase restores endothelium-dependent arteriolar dilatation during acute infusion of nicotine.

    PubMed

    Mayhan, W G; Sharpe, G M

    1998-10-01

    We previously showed [Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H2337-H2342, 1997] that nicotine impairs endothelium-dependent arteriolar dilatation. However, mechanisms that accounted for the effect of nicotine on endothelium-dependent vasodilatation were not examined. Thus the goal of this study was to examine the role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity. We measured diameter of cheek pouch resistance arterioles (approximately 50 micrometer diameter) in response to endothelium-dependent (ACh and ADP) and -independent (nitroglycerin) agonists before and after infusion of vehicle or nicotine in the absence or presence of superoxide dismutase. ACh, ADP, and nitroglycerin produced dose-related dilatation of cheek pouch arterioles before infusion of vehicle or nicotine. Infusion of vehicle, in the absence or presence of superoxide dismutase (150 U/ml), did not alter endothelium-dependent or -independent arteriolar dilatation. In contrast, infusion of nicotine (2 microgram . kg-1 . min-1) impaired endothelium-dependent, but not -independent, arteriolar dilatation. In addition, the effect of nicotine on endothelium-dependent vasodilatation was reversed by topical application of superoxide dismutase. We suggest that nicotine impairs endothelium-dependent arteriolar dilatation via an increase in the synthesis/release of oxygen-derived free radicals.

  4. An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions.

    PubMed

    Trauth, J A; Seidler, F J; Slotkin, T A

    2000-06-01

    Nearly all smokers begin tobacco use in adolescence, and approximately 25% of US teenagers are daily smokers. Prenatal nicotine exposure is known to produce brain damage, to alter synaptic function and to cause behavioral anomalies, but little or no work has been done to determine if the adolescent brain is also vulnerable. We examined the effect of adolescent nicotine exposure on indices of cell damage in male and female rats with an infusion paradigm designed to match the plasma levels found in human smokers or in users of the transdermal nicotine patch. Measurements were made of DNA and protein as well as expression of mRNAs encoding genes involved in differentiation and apoptosis (p53, c-fos) in cerebral cortex, midbrain and hippocampus. Following nicotine treatment from postnatal days 30-47.5, changes in macromolecular constituents indicative of cell loss (reduced DNA) and altered cell size (protein/DNA ratio) were seen across all three brain regions. In addition, expression of p53 showed region- and gender-selective alterations consistent with cell damage; c-fos, which is constitutively overexpressed after gestational nicotine exposure, was unaffected with the adolescent treatment paradigm. Although these measures indicate that the fetal brain is more vulnerable to nicotine than is the adolescent brain, the critical period for nicotine-induced developmental neurotoxicity clearly extends into adolescence. Effects on gene expression and cell number, along with resultant or direct effects on synaptic function, may contribute to increased addictive properties and long-term behavioral deficits. PMID:10837795

  5. Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

    PubMed Central

    Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

  6. Dependence on Tobacco and Nicotine Products: A Case for Product-Specific Assessment

    PubMed Central

    Eissenberg, Thomas

    2012-01-01

    The International Classification of Diseases and the Diagnostic and Statistical Manual for diagnosing tobacco/nicotine dependence emphasize the dependence-producing drug nicotine. These diagnostic tools have been challenged on grounds of poor predictive validity, and they do not differentiate across various forms of nicotine-containing products. In fact, nicotine-containing products (e.g., tobacco cigarettes, smokeless tobacco [ST], waterpipe, electronic cigarettes [ECIGs], and nicotine replacement [NR] products) have very different characteristics both in terms of sensory and behavioral involvement and also in pharmacokinetic and pharmacodynamic effects. For example, a cigarette and a nicotine patch are very different on almost every one of these dimensions. When ability to stop using a nicotine/tobacco product is used as a criterion for dependence, success rates vary considerably across products: Tobacco cigarette cessation is more difficult than ST cessation that in turn is more difficult than NR product cessation. Based on these results, we hypothesize that there is a continuum of dependence as much as there is a continuum of harm, with tobacco cigarettes and NR products on opposite ends of both continua and other products (waterpipe and ECIGs) somewhere in between. In order to capture more precisely the dependence produced by both nicotine and its administration forms, product-specific instruments may be required. The pros and cons of this approach are discussed. PMID:22459798

  7. Facilitation of cortico-amygdala synapses by nicotine: activity-dependent modulation of glutamatergic transmission.

    PubMed

    Jiang, Li; Role, Lorna W

    2008-04-01

    The basolateral nucleus of the amygdala (BLA) receives cholinergic innervation from the basal forebrain and nicotine, via activation of neuronal nicotinic acetylcholine receptors (nAChRs), can improve performance in amygdala-based learning tasks. We tested the hypothesis that acute and prenatal nicotine exposure modulates cortico-amygdala synaptic transmission. We found that low-dose, single-trial exposures to nicotine can elicit lasting facilitation, the extent of which is dependent on the level of stimulation of the cortical inputs to the BLA. In addition, sustained facilitation is ablated by prenatal exposure to nicotine. This study examined synaptic transmission in 238 patch-clamp recordings from BLA neurons in acute slice from mouse brain. Pharmacological studies in wild-type and nAChR subunit knock-out mice reveal that activation of presynaptic alpha 7, containing (alpha 7*) and non-alpha 7* nAChRs, facilitates glutamatergic transmission in an activity-dependent manner. Without prior stimulation, application of nicotine elicits modest and transient facilitation of glutamatergic postsynaptic currents (PSCs) in about 40% of BLA neurons. With low-frequency stimulation of cortical inputs nicotine elicits robust facilitation of transmission at about 60% of cortico-BLA synapses and synaptic strength remains elevated at about 40% of these connections for >15 min after nicotine washout. Following paired-pulse stimulation nicotine elicits long-lasting facilitation of glutamatergic transmission at about 70% of cortico-BLA connections. Nicotine reduces the threshold for activation of long-term potentiation of cortico-BLA synapses evoked by patterned stimulation. Prenatal exposure to nicotine reduced subsequent modulatory responses to acute nicotine application.

  8. Randomized Clinical Trial of the Efficacy of Bupropion Combined with Nicotine Patch in the Treatment of Adolescent Smokers

    ERIC Educational Resources Information Center

    Killen, Joel D.; Robinson, Thomas N.; Ammerman, Seth; Hayward, Chris; Rogers, Jayna; Stone, Christi; Samuels, Deanne; Levin, Sara K.; Green, Sarah

    2004-01-01

    Adolescent smokers (N = 211) were randomized to 1 of 2 groups: (a) nicotine patch plus bupropion SR (sustained release; 150 mg per day) or (b) nicotine patch plus placebo. Group skills training sessions were conducted each week by research staff. Abstinence rates at Weeks 10 and 26 were as follows: (a) patch plus bupropion, 23% and 8%, (b) patch…

  9. Exhaled carbon monoxide levels among Malaysian male smokers with nicotine dependence.

    PubMed

    Guan, Ng Chong; Ann, Anne Yee Hway

    2012-01-01

    We studied the use of exhaled carbon monoxide (CO) to identify nicotine dependence among adult Malaysian male smokers. We conducted a cross-sectional study among 107 male smoking staff at a university hospital. We measured their exhaled CO using a piCO+ Smokerlyzer and diagnosed nicotine dependence using a Mini-International Neuropsychiatric Interview (MINI). The optimal cut-off value for exhaled CO was determined. The correlation between exhaled CO level and the Fagerstrom Test for Nicotine Dependence (FTND) was also assessed. The mean exhaled CO level among subjects with nicotine dependence (15.78 ppm) was significantly higher than subjects without nicotine dependence (9.62 ppm). The cut-off value used to identify smokers with nicotine dependence was set at 10 ppm (specificity = 0.721, sensitivity = 0.731, positive predictive value = 0.817 and negative predictive value = 0.617). Psychometric properties were stable with various durations of smoking. Exhaled CO correlated positively with FTND scores (Pearson's rho = 0.398, p = 0.01). Our findings show exhaled CO can be used to identify nicotine dependence among adult Malaysian male smokers.

  10. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline.

    PubMed

    Foulds, J

    2006-05-01

    Smoking cessation has major health benefits for men and women of all ages. However, most smokers are addicted to nicotine and fail repeatedly in their attempts to quit. Stimulation of nicotinic receptors in the brain, particularly alpha4beta2 receptors, releases dopamine in the meso-limbic area of the brain and is reinforcing. Nicotine abstinence reduces dopamine release, and this is associated with withdrawal symptoms and craving for nicotine. Eight current pharmacotherapies--bupropion, nortriptyline, clonidine and nicotine patch, gum, inhaler, lozenge and nasal spray--are moderately effective aids to smoking cessation. Each is significantly better than placebo, but approximately 80% of patients using one of these medications return to smoking within the first year. Varenicline, a specific alpha4beta2 nicotinic receptor partial agonist, is a new pharmacotherapy that stimulates dopamine and simultaneously blocks nicotine receptors. Phase II and III trials have yielded promising results suggesting that varenicline could be an important advance in the treatment of nicotine dependence. PMID:16700857

  11. The shared role of oxidative stress and inflammation in major depressive disorder and nicotine dependence.

    PubMed

    Nunes, Sandra Odebrecht Vargas; Vargas, Heber Odebrecht; Prado, Eduardo; Barbosa, Decio Sabbatini; de Melo, Luiz Picoli; Moylan, Steven; Dodd, Seetal; Berk, Michael

    2013-09-01

    Nicotine dependence is common in people with mood disorders; however the operative pathways are not well understood. This paper reviews the contribution of inflammation and oxidative stress pathways to the co-association of depressive disorder and nicotine dependence, including increased levels of pro-inflammatory cytokines, increased acute phase proteins, decreased levels of antioxidants and increased oxidative stress. These could be some of the potential pathophysiological mechanisms involved in neuroprogression. The shared inflammatory and oxidative stress pathways by which smoking may increase the risk for development of depressive disorders are in part mediated by increased levels of pro-inflammatory cytokines, diverse neurotransmitter systems, activation the hypothalamic-pituitary-adrenal (HPA) axis, microglial activation, increased production of oxidative stress and decreased levels of antioxidants. Depressive disorder and nicotine dependence are additionally linked imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway that contribute to neuroprogression. These pathways provide a mechanistic framework for understanding the interaction between nicotine dependence and depressive disorder.

  12. Olfactory Cue-reactivity in Nicotine-Dependent Adult Smokers

    PubMed Central

    Cortese, Bernadette M.; Uhde, Thomas W.; LaRowe, Steven D.; Stein, Sarah V.; Freeman, W. Connor; McClernon, F. Joseph; Brady, Kathleen T.; Hartwell, Karen J.

    2014-01-01

    Cue-elicited reactivity is a significant factor in relapse during smoking quit attempts. Previous research has focused primarily on visual smoking cues, with very limited research examining reactivity to olfactory triggers. Twenty-six adult, non-treatment seeking, nicotine-dependent smokers were exposed to seven odorants during a cue-reactivity session measuring heart rate, skin conductance, and subjective craving. Cues included 2 cigarette odors (fresh tobacco and cigarette smoke), 2 odors previously identified as smoking-related (freshly mowed grass and coffee), 2 odors previously identified as unrelated to smoking (lavender and burned rubber), and 1 odorless control (propylene glycol). Pairwise comparisons demonstrated that subjective intensity of craving was significantly higher following exposure to the fresh tobacco odor compared to the odorless control (p<.01). A significant main effect for cue type on a physiological measure of arousal was also revealed, with a fresh tobacco odor-elicited significant increase in skin conductance level compared to the odorless control. No main effect of cue type on heart rate, however, was found (p=.25). The results of the present study indicate that cigarette odor is an effective olfactory cue that heightens both subjective craving and increases skin conductance in smokers. Future research is needed to evaluate whether avoidance of these odors, or extinction of responses to them, can reduce relapse risk during smoking quit attempts. PMID:25180553

  13. Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

    PubMed Central

    Galle-Treger, Lauriane; Suzuki, Yuzo; Patel, Nisheel; Sankaranarayanan, Ishwarya; Aron, Jennifer L.; Maazi, Hadi; Chen, Lin; Akbari, Omid

    2016-01-01

    Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β. Additionally, the specific α7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively, our data suggest that α7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma. PMID:27752043

  14. Nicotine dependence as a moderator of a quitline-based message framing intervention.

    PubMed

    Fucito, Lisa M; Latimer, Amy E; Carlin-Menter, Shannon; Salovey, Peter; Cummings, K Michael; Makuch, Robert W; Toll, Benjamin A

    2011-04-01

    High nicotine dependence is a reliable predictor of difficulty quitting smoking and remaining smoke-free. Evidence also suggests that the effectiveness of various smoking cessation treatments may vary by nicotine dependence level. Nicotine dependence, as assessed by Heaviness of Smoking Index baseline total scores, was evaluated as a potential moderator of a message-framing intervention provided through the New York State Smokers' Quitline (free telephone based service). Smokers were exposed to either gain-framed (n=810) or standard-care (n=1222) counseling and printed materials. Those smoking 10 or more cigarettes per day and medically eligible were also offered a free 2-week supply of nicotine patches, gum, or lozenge. Smokers were contacted for follow-up interviews at 3 months by an independent survey group. There was no interaction of nicotine dependence scores and message condition on the likelihood of achieving 7-day point prevalence smoking abstinence at the 3-month follow-up contact. Among continuing smokers at the 3-month follow-up, smokers who reported higher nicotine dependence scores were more likely to report smoking more cigarettes per day and this effect was greater in response to standard-care messages than gain-framed messages. Smokers with higher dependence scores who received standard-care messages also were less likely to report use of nicotine medications compared with less dependent smokers, while there was no difference in those who received gain-framed messages. These findings lend support to prior research demonstrating nicotine dependence heterogeneity in response to message framing interventions and suggest that gain-framed messages may result in less variable smoking outcomes than standard-care messages. PMID:21036492

  15. Peer Smoking and the Nicotinic Receptor Genes: An Examination of Genetic and Environmental Risks for Nicotine Dependence

    PubMed Central

    Johnson, Eric O.; Chen, Li-Shiun; Breslau, Naomi; Hatsukami, Dorothy; Robbins, Tania; Saccone, Nancy L.; Grucza, Richard A.; Bierut, Laura J.

    2010-01-01

    Background Peer smoking provides a socially reinforcing context of friends’ encouragement and approval that contributes to smoking behavior. Twin studies show correlations and interactions between peer substance use and genetic liability for substance use. However, none examined specific genes. Here we test the hypothesis that the nicotinic receptor genes CHRNA5 (rs16969968), CHRNA3 (rs578776), CHRNB3 (rs13277254), and CHRND (rs12466358) modify the risk for nicotine dependence (ND) associated with peer smoking. Methods Cases of current nicotine dependence (FTND ≥ 4) and smoking-exposed (smoked 100+ cigarettes lifetime), but non-dependent controls (lifetime FTND = 0) came from the Collaborative Genetic Study of Nicotine Dependence (n=2,038). Peer smoking was retrospectively assessed for grades 9–12. Results Peer smoking and the four SNPs were associated with ND. A statistically significant interaction was found between peer smoking and rs16969968 (p = 0.0077). Overall risk of ND was highest for the rs16969968 AA genotype. However, variance in ND attributable to peer smoking was substantially lower among those with the AA genotype at rs16969968 than the lower risk genotypes: AA = 2.5%, GA/AG = 11.2%, GG = 14.2%; p ≤ 0.004. Conclusions Peer smoking had a substantially lower effect on ND among those with the high risk AA genotype at the functional SNP rs16969968 (CHRNA5) than among those with lower risk genotypes. Such results highlight the possibility that given drug exposure those with specific genetic risks may be less affected by social contexts and intervention strategies focused on social factors could have less influence on those at highest genetic risk. PMID:20840187

  16. [Psychometric properties of the Nicotine Dependence Syndrome Scale (NDSS) in a sample of smokers treated for their alcohol dependence].

    PubMed

    Becoña, Elisardo; Nogueiras, Luis; Flórez, Gerardo; Alvarez, Sandra; Vázquez, Dolores

    2010-01-01

    The assessment of nicotine dependence with brief instruments is of great relevance for the better detection of this disorder. Here we present the results with the Nicotine Dependence Syndrome Scale (NDSS) by Shiffman, Waters and Hickcox (2004) in a sample of 183 patients treated at an Alcohol Dependence Unit who were also cigarette smokers. The results indicate that the general factor which evaluates nicotine dependence (NDSS-T) has good reliability (Cronbach's alpha = 0.80). Factor analysis identifies four of the five factors proposed in the original version, those of drive, priority, continuity and stereotypy. Reliability of the scales derived ranges from very good (0.80) to moderate (0.63). The NDSS-T correlates significantly with the Fagerström Tolerance Questionnaire (FTQ), with the DSM-IV criteria for nicotine dependence assessed through the SCID, and with the number of cigarettes smoked per day. The ROC curves indicate an NDSS-T score of 0.80 under the curve (0.70 for the FTND), showing that it adequately predicts nicotine dependence. This study confirms the utility of this new instrument for assessing nicotine dependence in smokers who also abuse or depend upon alcohol.

  17. Gestational IV nicotine produces elevated BDNF in the mesocorticolimbic dopamine system of adolescent rat offspring

    PubMed Central

    Harrod, Steven B.; Lacy, Ryan T.; Zhu, Jun; Hughes, Benjamin A.; Perna, Marla K.; Brown, Russell W.

    2015-01-01

    Maternal smoking during pregnancy is associated with enduring psychopathology, such as increased likelihood of substance use, in offspring. Various animal models demonstrate that continuous nicotine exposure produces teratogenic effects in offspring, as well. In the present experiment, a novel intravenous (IV) exposure model was utilized to determine if gestational nicotine (GN) treatment produced alterations in methamphetamine-induced sensitization and the expression of brain derived neurotrophic factor (BDNF) in the mesocorticolimbic dopamine system of adolescent offspring. Dams were injected with IV saline or nicotine (0.05 mg/kg/injection) 3x/day on gestational days 8–21. Habituation was measured on postnatal day (PND) 25–27 and baseline activity on PND 28. On PND 29–35, offspring were injected with saline or methamphetamine (0.3 mg/kg) and locomotor activity was measured after the first and seventh injections. On PND 36, brains were removed, flash frozen, and BDNF protein levels in the nucleus accumbens (NAcc), dorsal striatum (Str), frontal cortex (FC), and hippocampus (Hipp) were analyzed. GN did not affect habituation or the induction of methamphetamine-induced sensitization. Interestingly, GN, but not adolescent methamphetamine treatment, elevated levels of BDNF in the NAcc and Str; however, the GN-induced increase in BDNF in the FC was attenuated by adolescent methamphetamine treatment. Both GN and adolescent methamphetamine treatment increased BDNF in the Hipp. These findings indicate that GN exposure will result in increased levels of BDNF protein throughout the mesocorticolimbic dopamine system during adolescent development, and suggests that methamphetamine abuse will modulate the expression of BDNF in motivational circuitries of adolescent offspring exposed to GN. PMID:21990022

  18. Methods for smoking cessation and treatment of nicotine dependence.

    PubMed

    Balbani, Aracy Pereira Silveira; Montovani, Jair Cortez

    2005-01-01

    Smoking is related to 30% of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS), enhances alertness and reduces the appetite. A 50% reduction of nicotine consumption may trigger withdrawal symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy) and second-line (clonidine and nortriptyline) drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates. PMID:16878254

  19. Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal

    PubMed Central

    Ashare, Rebecca L; Schmidt, Heath D

    2014-01-01

    Introduction Current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, there is a clear need to develop novel antismoking medications. Nicotine withdrawal is associated with cognitive impairments that predict smoking relapse. It has been proposed that these cognitive deficits are a hallmark of nicotine withdrawal that could be targeted in order to prevent smoking relapse. Thus, pharmacotherapies that increase cognitive performance during nicotine withdrawal may represent potential smoking cessation agents. Areas covered The authors review the clinical literature demonstrating that nicotine withdrawal is associated with deficits in working memory, attention and response inhibition. They then briefly summarize different classes of compounds and strategies to increase cognitive performance during nicotine withdrawal. Particular emphasis has been placed on translational research in order to highlight areas for which there is strong rationale for pilot clinical trials of potential smoking cessation medications. Expert opinion There is emerging evidence that supports deficits in cognitive function as a plausible nicotine withdrawal phenotype. The authors furthermore believe that the translational paradigms presented here may represent efficient and valid means for the evaluation of cognitive-enhancing medications as possible treatments for nicotine dependence. PMID:24707983

  20. The alpha7 nicotinic acetylcholine receptor subtype mediates nicotine protection against NMDA excitotoxicity in primary hippocampal cultures through a Ca(2+) dependent mechanism.

    PubMed

    Dajas-Bailador, F A; Lima, P A; Wonnacott, S

    2000-10-01

    Neuronal nicotinic acetylcholine receptors (nAChR) have been suggested to play a role in a variety of modulatory and regulatory processes, including neuroprotection. Here we have characterized the neuroprotective effects of nicotine against an excitotoxic insult in primary hippocampal cultures. Exposure of hippocampal neurons to 200 microM NMDA for 1 h decreased cell viability by 25+/-5%, an effect blocked by NMDA receptor antagonists. Nicotine (10 microM) counteracted the NMDA-induced cell death when co-incubated with NMDA or when present subsequent to the NMDA treatment. Nicotine protection was prevented by 1 microM MLA, confirming that it was mediated by nAChR, and by 1 microM alpha-bungarotoxin, demonstrating that the alpha7 nAChR subtype was responsible. Both the NMDA evoked neurotoxicity and nicotine neuroprotection were Ca(2+)-dependent. In Fura-2-loaded hippocampal neurons, nicotine (10 microM) and NMDA (200 microM) acutely increased intracellular resting Ca(2+) from 70 nM to 200 and 500 nM, respectively. Responses to NMDA were unaffected by the presence of nicotine. (45)Ca(2+) uptake after a 1 h exposure to nicotine or NMDA also demonstrated quantitative differences between the two drugs. This study demonstrates that the alpha7 subtype of nAChR can support neuronal survival after an excitotoxic stimulus, through a Ca(2+) dependent mechanism that operates downstream of NMDA receptor activation.

  1. Involvement of dorsal hippocampal and medial septal nicotinic receptors in cross state-dependent memory between WIN55, 212-2 and nicotine or ethanol in mice.

    PubMed

    Alijanpour, S; Rezayof, A

    2013-08-15

    The present study examined whether nicotinic acetylcholine receptors (nAChRs) of the CA1 regions of the dorsal hippocampus and medial septum (MS) are involved in cross state-dependent memory retrieval between WIN55, 212-2 (WIN, a non-selective CB1/CB2 receptor agonist) and nicotine or ethanol. Memory retrieval was measured in one-trial step-down type passive avoidance apparatus in male adult mice. Pre-training intraperitoneal administration of WIN (0.1-1mg/kg) dose-dependently impaired memory retrieval when it was tested 24h later. Pre-test systemic administration of nicotine (0.6 and 0.7mg/kg, s.c.) or ethanol (0.5g/kg, i.p.) improved WIN-induced memory impairment, suggesting a cross state-dependent memory retrieval between the drugs. Pre-test intra-CA1 microinjection of nicotine (1 and 2μg/mouse) before systemic administration of an ineffective dose of nicotine (0.5mg/kg, s.c.) or ethanol (0.25g/kg) significantly reversed WIN-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (1 and 3μg/mouse) inhibited cross state-dependent memory between WIN and nicotine or ethanol. Moreover, pre-test intra-MS microinjection of nicotine (1 and 2μg/mouse) in combination with systemic administration of a lower dose of nicotine (0.5mg/kg), but not ethanol (0.25g/kg), improved memory impairment induced by pre-training administration of WIN. On the other hand, in the animals that received pre-training WIN and pre-test systemic administration of nicotine (0.7mg/kg), but not ethanol (0.5g/kg), pre-test intra-MS microinjection of mecamylamine (1-5μg/mouse) inhibited WIN-nicotine state-dependent memory retrieval. It should be noted that pre-test intra-CA1 or intra-MS microinjection of nicotine or mecamylamine by itself had no effect on memory retrieval and also could not reverse memory impairment induced by pre-training administration of WIN. It can be concluded that WIN and nicotine or WIN and ethanol can induce state-dependent memory retrieval. In

  2. Cigarette smoking, nicotine dependence and anxiety disorders: a systematic review of population-based, epidemiological studies

    PubMed Central

    2012-01-01

    Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective), the population assessed (random sample versus clinical population) and diagnostic instrument utilized. Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD)) for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders. Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder), although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified. Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as increasing the risk of

  3. Examining the Nature of the Association Between Attention-Deficit/Hyperactivity Disorder and Nicotine Dependence: A Familial Risk Analysis

    PubMed Central

    Biederman, Joseph; Petty, Carter R.; Hammerness, Paul; Woodworth, K. Yvonne; Faraone, Stephen V.

    2013-01-01

    Objective The main aim of this study was to use familial risk analysis to examine the association between attention-deficit/hyperactivity disorder (ADHD) and nicotine dependence. Methods Subjects were children with (n = 257) and without (n = 229) ADHD of both sexes ascertained form pediatric and psychiatric referral sources and their first-degree relatives (N = 1627). Results Nicotine dependence in probands increased the risk for nicotine dependence in relatives irrespective of ADHD status. There was no evidence of cosegregation or assortative mating between these disorders. Patterns of familial risk analysis suggest that the association between ADHD and nicotine dependence is most consistent with the hypothesis of independent transmission of these disorders. Conclusions These findings may have important implications for the identification of a subgroup of children with ADHD at high risk for nicotine dependence based on parental history of nicotine dependence. PMID:23461889

  4. BAG2 expression dictates a functional intracellular switch between the p38-dependent effects of nicotine on tau phosphorylation levels via the α7 nicotinic receptor.

    PubMed

    de Oliveira, Adriele Silva Alves; Santiago, Fernando Enrique; Balioni, Laiz Furlan; Ferrari, Merari de Fatima Ramires; Almeida, Maria Camila; Carrettiero, Daniel Carneiro

    2016-01-01

    The histopathological hallmarks present in Alzheimer's disease (AD) brain are plaques of Aβ peptide, neurofibrillary tangles of hyperphosphorylated tau protein, and a reduction in nicotinic acetylcholine receptor (nAChR) levels. The role of nAChRs in AD is particularly controversial. Tau protein function is regulated by phosphorylation, and its hyperphosphorylated forms are significantly more abundant in AD brain. Little is known about the relationship between nAChR and phospho-tau degradation machinery. Activation of nAChRs has been reported to increase and decrease tau phosphorylation levels, and the mechanisms responsible for this discrepancy are not presently understood. The co-chaperone BAG2 is capable of regulating phospho-tau levels via protein degradation. In SH-SY5Y cell line and rat primary hippocampal cell culture low endogenous BAG2 levels constitute an intracellular environment conducive to nicotine-induced accumulation of phosphorylated tau protein. Further, nicotine treatment inhibited endogenous expression of BAG2, resulting in increased levels of phosphorylated tau indistinguishable from those induced by BAG2 knockdown. Conversely, overexpression of BAG2 is conducive to a nicotine-induced reduction in cellular levels of phosphorylated tau protein. In both cases the effect of nicotine was p38MAPK-dependent, while the α7 antagonist MLA was synthetic to nicotine treatment, either increasing levels of phospho-Tau in the absence of BAG2, or further decreasing the levels of phospho-Tau in the presence of BAG2. Taken together, these findings reconcile the apparently contradictory effects of nicotine on tau phosphorylation by suggesting a role for BAG2 as an important regulator of p38-dependent tau kinase activity and phospho-tau degradation in response to nicotinic receptor stimulation. Thus, we report that BAG2 expression dictates a functional intracellular switch between the p38-dependent functions of nicotine on tau phosphorylation levels via the α7

  5. Nicotine dependence and psychosis in Bipolar disorder and Schizoaffective disorder, Bipolar Type

    PubMed Central

    Estrada, Elena; Hartz, Sarah; Tran, Jeffrey; Hilty, Donald; Sklar, Pamela; Smoller, Jordan W.; Pato, Carlos N.; Pato, Michele T.

    2016-01-01

    Objective Patients with Bipolar disorder smoke more than the general population. Smoking negatively impacts mortality and clinical course in Bipolar disorder patients. Prior studies have shown contradictory results regarding the impact of psychosis on smoking behavior in Bipolar disorder. We analyzed a large sample of Bipolar disorder and Schizoaffective disorder, Bipolar Type patients and predicted those with a history of psychosis would be more likely to be nicotine dependent. Methods Data from subjects and controls were collected from the Genomic Psychiatry Cohort (GPC). Subjects were diagnosed with Bipolar disorder without psychosis (N=610), Bipolar disorder with psychosis (N=1591), and Schizoaffective Disorder, Bipolar Type (N=1544). Participants were classified with or without nicotine dependence. Diagnostic groups were compared to controls (N=10065) using logistic regression. Results Among smokers (N=6157), those with Bipolar disorder had an increased risk of nicotine dependence (OR=2.5; p<0.0001). Patients with Bipolar disorder with psychosis were more likely to be dependent than Bipolar disorder patients without psychosis (OR=1.3; p=0.03). Schizoaffective disorder, Bipolar Type patients had more risk of nicotine dependence when compared to Bipolar disorder patients with or without psychosis (OR=1.2; p=0.02). Conclusions Bipolar disorder patients experiencing more severity of psychosis have more risk of nicotine dependence. PMID:26467098

  6. Dopamine-dependent modulation of rat globus pallidus excitation by nicotine acetylcholine receptors.

    PubMed

    Ríos, Alain; Barrientos, Rafael; Alatorre, Alberto; Delgado, Alfonso; Perez-Capistran, Teresa; Chuc-Meza, Eliezer; García-Ramirez, Martha; Querejeta, Enrique

    2016-02-01

    The globus pallidus (GP) coordinates information processing in the basal ganglia nuclei. The contribution of nicotinic cholinergic receptors (nAChRs) to the spiking activity of GP neurons is largely unknown. Several studies have reported that the effect of nAChRs in other nuclei depends on dopaminergic input. Via in vivo single unit extracellular recordings and intranuclear drug infusions, we analyzed the effects of local activation and blockade of nAChRs in neurons of both sham and 6-hydroxydopamine (6-OHDA)-lesioned rats. In sham rats, the local application of nicotine and edrophonium (an acetylcholinesterase inhibitor) increases GP neurons spiking rate. Local application of mecamylamine, a neuronal nicotinic cholinergic antagonist, diminishes pallidal neurons spiking rate, an effect not produced by d-tubocurarine, a peripheral nicotinic cholinergic antagonist. Moreover, mecamylamine blocks the excitatory effect evoked by nicotine and edrophonium. In 6-OHDA-lesioned rats, local infusion of nicotine does not change pallidal neurons firing rate. Our results show that there is a tonic cholinergic input to the GP that increases their spiking rate through the activation of nAChRs and that this effect depends on functional dopaminergic pathways.

  7. Acute effects of nicotine on alcohol cue-reactivity in nondependent and dependent smokers.

    PubMed

    McGrath, Daniel S; Peloquin, Marcel P; Ferdinand, Justin C; Barrett, Sean P

    2015-02-01

    Evidence from alcohol self-administration studies suggests that nicotine replacement therapy may influence subjective and behavioral responses to alcohol. However, its effect on alcohol cue-reactivity is unknown. The present study examined the impact of acutely administered nicotine on subjective responses to alcohol-focused pictorial stimuli. In a mixed within/between-subjects design, nondependent smokers (n = 51) and dependent smokers (n = 45) who socially drink were assigned to either a nicotine (4 mg) or placebo lozenge condition following overnight tobacco abstinence. Following lozenge absorption, participants viewed neutral images followed by alcohol-focused pictures. Craving measures for alcohol and tobacco were completed at baseline, following lozenge absorption, following neutral cues, and following alcohol cues. The presentation of alcohol cues increased alcohol-related craving relative to neutral cues, especially among men, but the administration of nicotine did not influence the magnitude of these effects. Nicotine lozenges were found to decrease intentions to smoke and withdrawal-related craving in dependent but not in nondependent smokers. Finally, the presentation of alcohol cues was found to increase intentions to smoke relative to neutral cues across participants regardless of lozenge condition. Findings suggest that although the presentation of alcohol cues can increase alcohol- and tobacco-related cravings in smokers, such effects do not appear to be affected by acute nicotine administration. PMID:25643027

  8. Adolescence is a period of development characterized by short- and long-term vulnerability to the rewarding effects of nicotine and reduced sensitivity to the anorectic effects of this drug.

    PubMed

    Natividad, Luis A; Torres, Oscar V; Friedman, Theodore C; O'Dell, Laura E

    2013-11-15

    This study compared nicotine intake and changes in food intake and weight gain in naïve adolescent, naïve adult, and adult rats that were exposed to nicotine during adolescence. An extended intravenous self-administration (IVSA) model was used whereby rats had 23-hour access to saline or increasing doses of nicotine (0.03, 0.06, and 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3-day periods of abstinence. Rats began IVSA as adolescents (PND 32-34) or adults (PND 75). A separate group of rats was exposed to nicotine via osmotic pumps (4.7 mg/kg) for 14 days during adolescence and then began nicotine IVSA as adults (PND 75). The rats that completed the nicotine IVSA regimen were also tested for nicotine-seeking behavior during extinction. The results revealed that nicotine intake was highest in adolescents followed by adults that were pre-exposed to nicotine during adolescence as compared to naïve adults. A similar pattern of nicotine-seeking behavior was observed during extinction. In contrast to nicotine intake, naïve adults displayed robust appetite and weight suppressant effects of nicotine, an effect that was absent in adolescents and adults that were pre-exposed to nicotine during adolescence. Our findings suggest that adolescence is a unique period of enhanced vulnerability to the reinforcing effects of nicotine. Although adolescents gain weight faster than adults, the food intake and weight suppressant effects of nicotine are reduced during adolescence. Importantly, our findings suggest that adolescent nicotine exposure produces long-lasting consequences that enhance nicotine reward and promote tolerance to the anorectic effects of this drug.

  9. Nicotine Dependence as a Mediator of Project EX's Effects to Reduce Tobacco Use in Scholars.

    PubMed

    Gonzálvez, María T; Espada, José P; Orgilés, Mireia; Morales, Alexandra; Sussman, Steve

    2016-01-01

    In Spain, 44% of 14-18-year-olds have smoked, and 12.5% have smoked cigarettes in the last 30 days. Nicotine is one of the most addictive substances, and can lead to serious addiction in adulthood with adverse consequences to one's health. School plays a relevant role in health promotion and preventing risk behaviors such as tobacco consumption. Despite the fact that some school-based tobacco cessation and prevention interventions prove to be effective for their purposes, there is a lack of understanding as to why these programs succeed or fail. This longitudinal study aims to test the nicotine dependence (ND) as a mediator of Project EX's effect - a tobacco-use cessation program developed for high school youth to reduce tobacco consumption in scholars. Six high schools located in the Mediterranean coast were randomized for the participation of the program (Spanish version of Project EX) or a waiting-list group with baseline, immediate-posttest, and 12-month follow-up assessments. At baseline, 1,546 adolescents aged 14-21 years old (mean age: 15.28; SD = 1.20; 46% were women) were evaluated by self-administered tests on tobacco consumption and ND. A biomarker of smoke inhalation - a measurement of exhaled carbon monoxide (ECM) - was used. Participants who were smokers (N = 501; 32%) were selected for this study. Mediation analyses were conducted using the PROCESS v2.12 macro for Windows. The significant criterion was p ≤ 0.05, and 5,000 samples were used for bias-corrected bootstrap confidence intervals. Results indicated that Project EX indirectly decreased the number of cigarettes smoked in the last month, the number of cigarettes smoked within the last 7 days, the number of daily cigarettes, and ECM level at 12-month follow up through decreasing the level of ND in the short-term. This is the first Spanish study that explores ND as a mediator of the long-term efficacy of Project EX to reduce tobacco consumption in adolescents. Results suggest that interventions

  10. Nicotine Dependence as a Mediator of Project EX's Effects to Reduce Tobacco Use in Scholars.

    PubMed

    Gonzálvez, María T; Espada, José P; Orgilés, Mireia; Morales, Alexandra; Sussman, Steve

    2016-01-01

    In Spain, 44% of 14-18-year-olds have smoked, and 12.5% have smoked cigarettes in the last 30 days. Nicotine is one of the most addictive substances, and can lead to serious addiction in adulthood with adverse consequences to one's health. School plays a relevant role in health promotion and preventing risk behaviors such as tobacco consumption. Despite the fact that some school-based tobacco cessation and prevention interventions prove to be effective for their purposes, there is a lack of understanding as to why these programs succeed or fail. This longitudinal study aims to test the nicotine dependence (ND) as a mediator of Project EX's effect - a tobacco-use cessation program developed for high school youth to reduce tobacco consumption in scholars. Six high schools located in the Mediterranean coast were randomized for the participation of the program (Spanish version of Project EX) or a waiting-list group with baseline, immediate-posttest, and 12-month follow-up assessments. At baseline, 1,546 adolescents aged 14-21 years old (mean age: 15.28; SD = 1.20; 46% were women) were evaluated by self-administered tests on tobacco consumption and ND. A biomarker of smoke inhalation - a measurement of exhaled carbon monoxide (ECM) - was used. Participants who were smokers (N = 501; 32%) were selected for this study. Mediation analyses were conducted using the PROCESS v2.12 macro for Windows. The significant criterion was p ≤ 0.05, and 5,000 samples were used for bias-corrected bootstrap confidence intervals. Results indicated that Project EX indirectly decreased the number of cigarettes smoked in the last month, the number of cigarettes smoked within the last 7 days, the number of daily cigarettes, and ECM level at 12-month follow up through decreasing the level of ND in the short-term. This is the first Spanish study that explores ND as a mediator of the long-term efficacy of Project EX to reduce tobacco consumption in adolescents. Results suggest that interventions

  11. [The Short Nicotine Dependence Syndrome Scale (NDSS-S) in Spanish smokers].

    PubMed

    Becoña, Elisardo; Fernández del Río, Elena; López, Ana; Míguez, María del Carmen; Castro, Josefina; Nogueiras, Luis; Flórez, Gerardo; Alvarez, Sandra; Vázquez, Dolores

    2011-02-01

    We present a brief scale derived from the Nicotine Dependence Syndrome Scale (NDSS). We used a sample of 1.061 daily smokers, which was obtained from five Primary Care Health Centers, a Unit of Alcoholism, and a Smoking Cessation Unit. All smokers were evaluated with the NDSS and the SCID to assess nicotine dependence according to DSM-IV criteria. The results indicate the existence of a general factor of nicotine dependence according to the NDSS. We selected the items with a higher factor loading (>.50), obtaining a short scale of 6 items. With this brief scale, we obtained results similar to those of the total scale in the diverse variables (sociodemographic and smoking) of the study. Scale reliability is satisfactory (a= .79), the correlation between the short and the total scale is very high (r=.95, p<.001) and the short scale discriminates the smokers in terms of cigarette consumption and nicotine dependence, as assessed with the SCID. The operation under the ROC curve is excellent (area under the curve .84). The data indicate the usefulness of this brief scale (NDSS-S) to assess nicotine dependence in smokers.

  12. Early postnatal nicotine exposure disrupts the α2* nicotinic acetylcholine receptor-mediated control of oriens-lacunosum moleculare cells during adolescence in rats.

    PubMed

    Chen, Kang; Nakauchi, Sakura; Su, Hailing; Tanimoto, Saki; Sumikawa, Katumi

    2016-02-01

    Maternal cigarette smoking during pregnancy and maternal nicotine exposure in animal models are associated with cognitive impairments in offspring. However, the underlying mechanism remains unknown. Oriens-lacunosum moleculare (OLM) cells expressing α2* nicotinic acetylcholine receptors (nAChRs) are an important component of hippocampal circuitry, gating information flow and long-term potentiation (LTP) in the CA1 region. Here we investigated whether early postnatal nicotine exposure alters the normal role of α2*-nAChR-expressing OLM cells during adolescence in rats. We found that early postnatal nicotine exposure significantly decreased not only the number of α2-mRNA-expressing interneurons in the stratum oriens/alveus, but also α2*-nAChR-mediated responses in OLM cells. These effects of nicotine were prevented by co-administration with the nonselective nAChR antagonist mecamylamine, suggesting that nicotine-induced activation, but not desensitization, of nAChRs mediates the effects. α2*-nAChR-mediated depolarization of OLM cells normally triggers action potentials, causing an increase in spontaneous inhibitory postsynaptic currents in synaptically connected pyramidal cells. However, these α2*-nAChR-mediated effects were profoundly reduced after early postnatal nicotine exposure, suggesting altered control of CA1 circuits by α2*-nAChR-expressing OLM cells. Furthermore, these effects were associated with altered excitatory neural activity and LTP as well as the loss of normal α2*-nAChR-mediated control of excitatory neural activity and LTP. These findings suggest the altered function of α2*-nAChR-expressing OLM cells as an important target of further study for identifying the mechanisms underlying the cognitive impairment induced by maternal smoking during pregnancy.

  13. Waterpipe tobacco smoking: what is the evidence that it supports nicotine/tobacco dependence?

    PubMed Central

    Aboaziza, Eiman; Eissenberg, Thomas

    2015-01-01

    Objective Waterpipe tobacco smoking (WTS) involves passing tobacco smoke through water prior to inhalation, and has spread worldwide. This spread becomes a public health concern if it is associated with tobacco-caused disease and if WTS supports tobacco/nicotine dependence. A growing literature demonstrates that WTS is associated with disability, disease and death. This narrative review examines if WTS supports nicotine/tobacco dependence, and is intended to help guide tobacco control efforts worldwide. Data sources PUBMED search using: ((“waterpipe” or “narghile” or “arghile” or “shisha” or “goza” or “narkeela” or “hookah” or “hubble bubble”)) AND (“dependence” or “addiction”). Study selection Excluded were articles not in English, without original data, and that were not topic-related. Thirty-two articles were included with others identified by inspecting reference lists and other sources. Data synthesis WTS and the delivery of the dependence-producing drug nicotine were examined, and then the extent to which the articles addressed WTS-induced nicotine/dependence explicitly, as well as implicitly with reference to criteria for dependence outlined by the WHO. Conclusions WTS supports nicotine/tobacco dependence because it is associated with nicotine delivery, and because some smokers experience withdrawal when they abstain from waterpipe, alter their behaviour in order to access a waterpipe and have difficulty quitting, even when motivated to do so. There is a strong need to support research investigating measurement of WTS-induced tobacco dependence, to inform the public of the risks of WTS, which include dependence, disability, disease and death, and to include WTS in the same public health policies that address tobacco cigarettes. PMID:25492935

  14. Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers

    PubMed Central

    Brasic, James R.; Contoreggi, Carlo; Cascella, Nicola; Mackowick, Kristen M.; Taylor, Richard; Rousset, Olivier; Willis, William; Huestis, Marilyn A.; Concheiro, Marta; Wand, Gary; Wong, Dean F.; Volkow, Nora D.

    2014-01-01

    The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward. PMID:25493427

  15. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    SciTech Connect

    Xu, Yuan Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  16. Opioid receptor types involved in the development of nicotine physical dependence in an invertebrate (Planaria) model.

    PubMed

    Raffa, Robert B; Baron, Steve; Bhandal, Jaspreet S; Brown, Tevin; Song, Kevin; Tallarida, Christopher S; Rawls, Scott M

    2013-11-01

    Recent data suggest that opioid receptors are involved in the development of nicotine physical dependence in mammals. Evidence in support of a similar involvement in an invertebrate (Planaria) is presented using the selective opioid receptor antagonist naloxone, and the more receptor subtype-selective antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (μ, MOR), naltrindole (δ, DOR), and nor-BNI (norbinaltorphimine) (κ, KOR). Induction of physical dependence was achieved by 60-min pre-exposure of planarians to nicotine and was quantified by abstinence-induced withdrawal (reduction in spontaneous locomotor activity). Known MOR and DOR subtype-selective opioid receptor antagonists attenuated the withdrawal, as did the non-selective antagonist naloxone, but a KOR subtype-selective antagonist did not. An involvement of MOR and DOR, but not KOR, in the development of nicotine physical dependence or in abstinence-induced withdrawal was thus demonstrated in a sensitive and facile invertebrate model.

  17. Neuronal calcium/calmodulin-dependent protein kinase II mediates nicotine reward in the conditioned place preference test in mice.

    PubMed

    Jackson, Kia J; Muldoon, Pretal P; Walters, Carrie; Damaj, Mohamad Imad

    2016-02-01

    Several recent studies have indicated the involvement of calcium-dependent mechanisms, in particular the abundant calcium-activated kinase, calcium/calmodulin-dependent kinase II (CaMKII), in behaviors associated with nicotine dependence in mice. Behavioral and biochemical studies have shown that CaMKII is involved in acute and chronic nicotine behaviors and nicotine withdrawal; however, evidence of a role for CaMKII in nicotine reward is lacking. Thus, the goal of the current study was to examine the role of CaMKII in nicotine reward. Using pharmacological and genetic tools, we tested nicotine conditioned place preference (CPP) in C57Bl/6 mice after administration of CaMKII antagonists and in α-CaMKII wild-type (+/+) and heterozygote (±) mice. CaMKII antagonists blocked expression of nicotine CPP, and the preference score was significantly reduced in α-CaMKII ± mice compared with their +/+ counterparts. Further, we assessed CaMKII activity in the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex, and hippocampus after nicotine CPP and found significant increases in CaMKII activity in the mouse VTA and NAc that were blocked by CaMKII antagonists. The findings from this study show that CaMKII mediates nicotine reward and suggest that increases in CaMKII activity in the VTA and NAc are relevant to nicotine reward behaviors.

  18. Paradoxical effects of injection stress and nicotine exposure experienced during adolescence on learning in a serial multiple choice (SMC) task in adult female rats.

    PubMed

    Renaud, Samantha M; Pickens, Laura R G; Fountain, Stephen B

    2015-01-01

    Nicotine exposure in adolescent rats has been shown to cause learning impairments that persist into adulthood long after nicotine exposure has ended. This study was designed to assess the extent to which the effects of adolescent nicotine exposure on learning in adulthood can be accounted for by adolescent injection stress experienced concurrently with adolescent nicotine exposure. Female rats received either 0.033 mg/h nicotine (expressed as the weight of the free base) or bacteriostatic water vehicle by osmotic pump infusion on postnatal days 25-53 (P25-53). Half of the nicotine-exposed rats and half of the vehicle rats also received twice-daily injection stress consisting of intraperitoneal saline injections on P26-53. Together these procedures produced 4 groups: No Nicotine/No Stress, Nicotine/No Stress, No Nicotine/Stress, and Nicotine/Stress. On P65-99, rats were trained to perform a structurally complex 24-element serial pattern of responses in the serial multiple choice (SMC) task. Four general results were obtained in the current study. First, learning for within-chunk elements was not affected by either adolescent nicotine exposure, consistent with past work (Pickens, Rowan, Bevins, and Fountain, 2013), or adolescent injection stress. Thus, there were no effects of adolescent nicotine exposure or injection stress on adult within-chunk learning typically attributed to rule learning in the SMC task. Second, adolescent injection stress alone (i.e., without concurrent nicotine exposure) caused transient but significant facilitation of adult learning restricted to a single element of the 24-element pattern, namely, the "violation element," that was the only element of the pattern that was inconsistent with pattern structure. Thus, adolescent injection stress alone facilitated violation element acquisition in adulthood. Third, also consistent with past work (Pickens et al., 2013), adolescent nicotine exposure, in this case both with and without adolescent

  19. [Treatment outcome in tobacco dependence after nicotine replacement therapy and group therapy].

    PubMed

    Górecka, D; Borak, J; Goljan, A; Gorzelak, K; Mańkowski, M; Zgierska, A

    1999-01-01

    The deletorious health effects of smoking are generally known. In spite of that, great numbers of people still smoke tobacco in the whole world. It is primarily due to the addictive properties of nicotine. Cigarette smoking is also dependent on various social and psychologic factors making quitting very difficult. Among various treatment modalities for tobacco dependence we aimed to assess the efficacy of nicotine replacement therapy (NRT) vs group therapy. 325 subjects smoking at least 15 cigarettes/day for more than 3 years were studied. They were allocated to group therapy (neurolinguistic programming) or NRT (gum or patch) at their will. Non-smoking was validated at each of follow-up visits, at 1 and 2 weeks 1, 3, 6, 12 months by measuring CO in expired air. All groups were matched in age, smoking history and nicotine dependence. The best quit rate was observed as a result of group therapy (41% at 1 year, p. < 0.001) as compared to nicotine patch (2%) and nicotine gum (9%). PMID:10497441

  20. Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males

    PubMed Central

    Xie, Pingxing; Kranzler, Henry R; Zhang, Huiping; Oslin, David; Anton, Raymond F; Farrer, Lindsay A; Gelernter, Joel

    2012-01-01

    The relative importance of specific genetic and environmental factors in regulating nicotine dependence (ND) risk, including the effects on specific forms of childhood adversity on smoking risk, have been understudied. Genome-wide association studies and rodent models have demonstrated that the α5 nicotinic acetylcholine receptor gene (CHRNA5) is important in regulating nicotine intake. Childhood adversity increases the methylation level of the CHRNA5 promoter region in European Americans (EAs), an effect that was observed only in males (Zhang et al, submitted for publication). In view of this potential sex difference in the effects of early life experience on smoking, we investigated the presence of a sex-specific gene-by-environment effect of this marker on ND risk. A nonsynonymous SNP in CHRNA5 previously associated to ND and several related traits, rs16969968, was genotyped in 2206 EAs (1301 men and 905 women). The main and interactive effects of childhood adversity and rs16969968 genotype on diagnosis of ND and ND defined by dichotomized Fagerstrom test for ND (FTND) scores were explored. Men and women were analyzed separately to test for sex differences. Childhood adversity significantly increased ND risk in both sexes, and the effect in women was twice than that in men. Significant interactive effects of childhood adversity and rs16969968 genotype were observed in men (ND: OR=1.80, 95% CI=1.18–2.73, P=0.0044; FTND: OR=1.79, 95% CI=1.11–2.88, P=0.012). No interaction was found in women. This study provides evidence of a sex-specific gene × environment effect of CHRNA5 and childhood adversity on the risk for ND. PMID:22012472

  1. Do Smokers Know What We're Talking about? The Construct Validity of Nicotine Dependence Questionnaire Measures

    ERIC Educational Resources Information Center

    Japuntich, Sandra J.; Piper, Megan E.; Schlam, Tanya R.; Bolt, Daniel M.; Baker, Timothy B.

    2009-01-01

    Few studies have examined whether nicotine dependence self-report questionnaires can predict specific behaviors and symptoms at specific points in time. The present study used data from a randomized clinical trial (N = 608; M. E. Piper et al., 2007) to assess the construct validity of scales and items from 3 nicotine dependence measures: the…

  2. Parent, sibling and peer influences on smoking initiation, regular smoking and nicotine dependence. Results from a genetically informative design.

    PubMed

    Scherrer, Jeffrey F; Xian, Hong; Pan, Hui; Pergadia, Michele L; Madden, Pamela A F; Grant, Julia D; Sartor, Carolyn E; Haber, Jon Randolph; Jacob, Theodore; Bucholz, Kathleen K

    2012-03-01

    We sought to determine whether parenting, sibling and peer influences are associated with offspring ever smoking, regular smoking and nicotine dependence (ND) after controlling for familial factors. We used a twin-family design and data from structured diagnostic surveys of 1919 biological offspring (ages 12-32 years), 1107 twin fathers, and 1023 mothers. Offspring were classified into one of four familial risk groups based on twin fathers' and their co-twins' history of DSM-III-R nicotine dependence. Multivariate multinomial logistic regression was used to model familial risk, paternal and maternal parenting behavior and substance use, sibling substance use, and friend and school peer smoking, alcohol and drug use. Ever smoking was associated with increasing offspring age, white race, high maternal pressure to succeed in school, sibling drug use, and friend smoking, alcohol and drug use. Offspring regular smoking was associated with these same factors with additional contribution from maternal ND. Offspring ND was associated with increasing offspring age, male gender, biological parents divorce, high genetic risk from father and mother ND, maternal problem drinking, maternal rule inconsistency and sibling drug use, and friend smoking, alcohol and drug use. Friend smoking had the largest magnitude of association with offspring smoking. This effect remains after accounting for familial liability and numerous parent and sibling level effects. Smoking interventions may have greatest impact by targeting smoking prevention among peer groups in adolescent and young adult populations. PMID:22094168

  3. Maternal Nicotine Exposure During Late Gestation and Lactation Increases Anxiety-Like and Impulsive Decision-Making Behavior in Adolescent Offspring of Rat

    PubMed Central

    Lee, Hyunchan; Chung, Sooyeon; Noh, Jihyun

    2016-01-01

    Prenatal nicotine exposure over an entire pregnancy has been associated with an increased prevalence of hyperactivity, anxiety-like behavior and depression-like behavior in mature rats. However, the effects of maternal nicotine exposure in late gestation and lactation on the psychology and behavior of adolescent rat offspring are unclear. Thus, we investigated the effect of nicotine exposure during late gestation and lactation on anxiety-like and impulsive decision-making behavior in adolescent offspring of rat. Female rats were orally exposed to nicotine which is within range of plasma level of human chronic smokers during the period of third last period of gestation and lactation. When the offspring were weaned, we observed alterations in the anxiety-like behavior and decision-making ability of adolescent rat offspring using light/dark box test and T-maze delay-based cost-benefit decision-making task. The maternal consumption of nicotine reduced both the time spent in the light compartment and the number of transitions compared to nicotine-free rats. Moreover, such nicotine exposed adolescent offspring rats showed impulsive decision making which chose the instant reward in a decision-making situation. We found that nicotine exposure during late gestation and lactation induces an increase in anxiety-like and impulsive decision-making behavior at this developmental stage. These findings suggest that maternal nicotine-exposed offspring are at an increased risk of developing anxious and impulsive behavior.

  4. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

    PubMed

    Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

    2016-10-15

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects.

  5. Effects of adolescent nicotine and SR 147778 (Surinabant) administration on food intake, somatic growth and metabolic parameters in rats.

    PubMed

    Lamota, Laura; Bermudez-Silva, Francisco Javier; Marco, Eva-María; Llorente, Ricardo; Gallego, Araceli; Rodríguez de Fonseca, Fernando; Viveros, María-Paz

    2008-01-01

    Tobacco smoking and obesity are worldwide important health problems with a growing impact in adolescent and young adults. One of the consequences of nicotine withdrawal is an increase in body weight that can act as a risk factor to relapse. Experimental therapies with a cannabinoid receptor antagonist have been recently proposed for both cigarette smoking and complicated overweight. In the present study, we aimed to investigate metabolic and hormonal effects of chronic nicotine treatment (during treatment and in abstinence) in an animal model of adolescence as well as to address the pharmacological effects of the novel selective CB1 cannabinoid receptor antagonist, SR 147778 (Surinabant). Adolescence (postnatal days 37-44) and/or post-adolescence (postnatal days 45-59) administration of Surinabant reduced body weight gain, as well as plasma glucose levels and triglycerides. The drug also reduced insulin and leptin secretion, and increased adiponectin and corticosterone levels. The effects showed sexual dimorphisms and, in general, were more pronounced in females. Chronic exposure to nicotine (0.8 mg/kg), from postnatal days 30-44 did not result in overt effects on food intake or body weight gain. However, it altered certain responses to the administration of Surinabant, both when the two drugs were given simultaneously and when Surinabant was administered during the post-adolescence period, along nicotine withdrawal. The present results indicate that the endogenous cannabinoid system is active as a metabolic modulator during adolescence and that nicotine exposure can induce long-lasting effects on metabolic regulation, altering cannabinoid modulation of energy expenditure and metabolism.

  6. Does allowing adolescents to smoke at home affect their consumption and dependence?

    PubMed

    Luther, Emily J; Parzynski, Craig S; Jaszyna-Gasior, Maria; Bagot, Kara S; Royo, Marc B; Leff, Michelle K; Moolchan, Eric T

    2008-06-01

    Negative parental attitudes towards smoking decrease adolescent smoking initiation but limited research explores the relationship between parental attitudes and degree of adolescent smoking among established smokers. The aim of this study was to examine the relationship between parental allowance of smoking in the home and adolescent smoking behavior and level of dependence. Interviews from 408 youths seeking assistance to quit smoking showed that adolescents who were allowed to smoke at home smoked more cigarettes per day and had higher scores on the Fagerström Test of Nicotine Dependence than those not allowed to smoke at home. Studies that additionally evaluate parental smoking status and the temporal relationship of parental allowance of smoking with changes in adolescent smoking behavior are warranted to clarify public health implications of parental smoking interdictions. PMID:18272294

  7. Impact of Tobacco Control Policy on Quitting and Nicotine Dependence among Women in Five European Countries

    PubMed Central

    Allen, JA; Gritz, ER; Xiao, H; Rubenstein, R; Kralikova, Eva; Haglund, Margaretha; Heck, JE; Niaura, R; Vallone, DM

    2014-01-01

    Objective Describe differences in and factors associated with former smoking and nicotine dependence among women in Ireland, Sweden, France, Italy and the Czech Republic. Methods A cross-sectional, random digit dial telephone survey of 5000 women, ages 18 and older, conducted in 2008. Analyses were conducted using logistic regression models. Results Respondents from Ireland and Sweden had statistically significantly higher odds of having quit smoking within the 5 years prior to survey administration as compared with respondents from the Czech Republic. Current smokers from Ireland, Sweden, France and Italy are more nicotine dependent than those from the Czech Republic. Conclusions Respondents from countries with stronger tobacco control policies were more likely to be have quit smoking compared with those living in the Czech Republic. However, respondents in countries with some of the strongest policies (Ireland, Sweden, France and Italy) had higher odds of smoking within 30 minutes of waking, an established indicator of nicotine dependence. More research in this area is warranted, but this study suggests that: 1) now that the Czech Republic is beginning to implement strong tobacco control policy, they will likely achieve a rapid decline in population-level smoking; and 2) Ireland, Sweden, France, Italy and other countries with established, strong tobacco control policies would do well to consider what additional programs they can put in place to help their highly nicotine dependent population of smokers successfully quit. PMID:23152098

  8. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.

    PubMed

    Rose, Jed E; Behm, Frédérique M; Drgon, Tomas; Johnson, Catherine; Uhl, George R

    2010-01-01

    Improving and targeting nicotine replacement therapy (NRT) are cost-effective strategies for reducing adverse health consequences for smokers. Treatment studies document the efficacy of precessation NRT and support important roles for level of nicotine dependence and precessation smoking reduction in successful quitting. However, prior work has not identified the optimal precessation dose or means for personalizing NRT. Genome-wide association has identified groups of genomic markers associated with successful quitting, allowing us to develop a v1.0 "quit-success" genotype score. We now report influences of v1.0 quit-success genotype score, level of dependence and precessation smoking reduction in a smoking cessation trial that examined effects of 21 versus 42 mg/24 h precessation NRT. Four hundred seventy-nine smokers were randomized to 21 or 42 mg NRT, initiated 2 wks prior to target quit dates. We monitored self-reported abstinence and end-expired air carbon monoxide (CO). Genotyping used Affymetrix arrays (Santa Clara, CA, USA). The primary outcome was 10-wk continuous smoking abstinence. NRT dose, level of nicotine dependence and genotype scores displayed significant interactive effects on successful quitting. Successful abstinence also was predicted by CO reductions during precessation NRT. These results document ways in which smoking cessation strategies can be personalized based on levels of nicotine dependence, genotype scores and CO monitoring. These assessments, taken together, can help match most smokers with optimal NRT doses and help rapidly identify some who may be better treated using other methods.

  9. Functional connectivity analysis of resting-state fMRI networks in nicotine dependent patients

    NASA Astrophysics Data System (ADS)

    Smith, Aria; Ehtemami, Anahid; Fratte, Daniel; Meyer-Baese, Anke; Zavala-Romero, Olmo; Goudriaan, Anna E.; Schmaal, Lianne; Schulte, Mieke H. J.

    2016-03-01

    Brain imaging studies identified brain networks that play a key role in nicotine dependence-related behavior. Functional connectivity of the brain is dynamic; it changes over time due to different causes such as learning, or quitting a habit. Functional connectivity analysis is useful in discovering and comparing patterns between functional magnetic resonance imaging (fMRI) scans of patients' brains. In the resting state, the patient is asked to remain calm and not do any task to minimize the contribution of external stimuli. The study of resting-state fMRI networks have shown functionally connected brain regions that have a high level of activity during this state. In this project, we are interested in the relationship between these functionally connected brain regions to identify nicotine dependent patients, who underwent a smoking cessation treatment. Our approach is on the comparison of the set of connections between the fMRI scans before and after treatment. We applied support vector machines, a machine learning technique, to classify patients based on receiving the treatment or the placebo. Using the functional connectivity (CONN) toolbox, we were able to form a correlation matrix based on the functional connectivity between different regions of the brain. The experimental results show that there is inadequate predictive information to classify nicotine dependent patients using the SVM classifier. We propose other classification methods be explored to better classify the nicotine dependent patients.

  10. Attachment and Depression Differentially Influence Nicotine Dependence among Male and Female Undergraduates: A Preliminary Study.

    ERIC Educational Resources Information Center

    McChargue, Dennis E.; Cohen, Lee M.; Cook, Jessica W.

    2004-01-01

    The authors surveyed a convenience sample of 208 undergraduate students who reported that they smoked cigarettes. The primary hypothesis they tested was whether gender predicted nicotine dependence. They further tested whether depression and attachment would mediate or moderate this relationship. Hierarchical regression analyses with social…

  11. ADHD as a Serious Risk Factor for Early Smoking and Nicotine Dependence in Adulthood

    ERIC Educational Resources Information Center

    Matthies, Swantje; Holzner, Sebastian; Feige, Bernd; Scheel, Corinna; Perlov, Evgeniy; Ebert, Dieter; van Elst, Ludger Tebartz; Philipsen, Alexandra

    2013-01-01

    Objective: Tobacco smoking and ADHD frequently co-occur. So far, the bulk of research on the ADHD-smoking comorbidity has been done in children with ADHD and nonclinical adult samples. To assess smoking habits in adults with ADHD, the authors used the Fagerstrom Test for Nicotine Dependence (FTND). Method: In 60 adult outpatients, with an ADHD…

  12. D{sub 2} dopamine receptor gene and behavioral characteristics in nicotine dependence

    SciTech Connect

    Noble, E.P.; Fitch, R.J.; Syndulko, K.

    1994-09-01

    The D{sub 2} dopamine receptor (DRD2) A1 allele has been recently associated with nicotine dependence. In the present study, TaqI A alleles (the minor A1 and the major A2 allele) of the DRD2 were determined in medically-ill subjects. The sample was composed of 41 non-smokers (N), 69 ex-smokers (X) and 63 active smokers (A). The relationships of DRD2 alleles to personality (Eysenick`s Addictive Personality [AP]), depression and nicotine dependence (Fagerstroem) scores were ascertained. A significant (P = 0.002) group effect prevailed in the AP scores, with the A group having the highest scores. Moreover, a significant (P = 0.025) allele by group interaction was found, with A1 allelic subjects in group A showing the highest AP scores. Significant group effects were also found in both the depression (P = 0.0004) and the nicotine dependence (P = 0.0003) scores, with the A group again showing the highest scores. However, in contrast to the AP scores, no significant allele by group interaction was found either in the depression or the nicotine dependence scores. In conclusion, the present findings suggest a role for the DRD2 gene in personality of smokers. However, relationship of the DRD2 gene to the degree of depression or nicotine dependence was not found. The data indicate the importance of using behavioral and genetic variables in dissecting the complex set of variables associated with the smoking habit, and thus in achieving a better understanding of the biobehavioral bases of this addiction.

  13. Sustained Reduction of Nicotine Craving With Real-Time Neurofeedback: Exploring the Role of Severity of Dependence

    PubMed Central

    2013-01-01

    Background: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. Methods: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to “crave,” patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. Results: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. Conclusions: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods. PMID:23935182

  14. Tobacco Use and Nicotine Dependence among HIV-Infected and Uninfected Injection Drug Users

    PubMed Central

    Marshall, Mariah M.; Kirk, Gregory D.; Caporaso, Neil E.; McCormack, Meredith C.; Merlo, Christian A.; Hague, John C.; Mehta, Shruti H.; Engels, Eric A.

    2010-01-01

    Introduction Urban U.S. populations are burdened by intersecting epidemics of HIV-infection, injection drug use, and cigarette smoking. Given the substantial morbidity attributable to tobacco in these populations, we characterized smoking behaviors, nicotine addiction, and tobacco exposure among HIV-infected and HIV-uninfected injection drug users (IDUs) in Baltimore, Maryland. Methods Smoking behaviors among participants in the ALIVE Study were assessed using interviewer-administered questionnaires. Smoking history and nicotine dependence (Fagerstrom Index scores) were compared by HIV and drug injecting status. Serum cotinine (a nicotine metabolite) was measured for a sample of participants by enzyme immunoassay. Results Among 1,052 participants (29.7% HIV-infected, 39.8% active injectors), 85.2% were current smokers and 9.3% former smokers. Smoking prevalence, age at smoking initiation, and cumulative tobacco exposure were similar by HIV status. Median Fagerstrom scores of 4 for HIV-infected and HIV-uninfected smokers indicated moderate nicotine dependence. Daily cigarette consumption was identical by HIV status (median 10 cigarettes), although HIV-infected participants were less likely to smoke 1+ pack daily compared to HIV-uninfected participants (18.0% vs. 26.9%, p=0.001). Compared to former injectors, active injectors had higher smoking prevalence (90.5% vs. 81.7%, p=0.0001), greater daily cigarette consumption (30.7% vs. 19.6% smoked 1+ pack daily, p=0.0001), and slightly higher Fagerstrom scores (median 5 vs. 4). Cotinine levels paralleled self-reported cigarette consumption. Discussion Tobacco use is extremely common among inner city IDUs. Smoking behavior and nicotine dependence did not materially differ by HIV status but were associated with active drug injection. Cessation efforts should target the dual dependence of cigarettes and drugs experienced among this population. PMID:20875704

  15. L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway.

    PubMed

    Di, Xiaojing; Yan, Jingqi; Zhao, Yan; Chang, Yanzhong; Zhao, Baolu

    2012-12-01

    In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a conditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DHβE). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the α(4), β(2) and α(7) nicotine acetylcholine receptor (nAChR) subunits induced by nicotine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction.

  16. Acceptance of nicotine dependence treatment among currently depressed smokers.

    PubMed

    Haug, Nancy A; Hall, Sharon M; Prochaska, Judith J; Rosen, Amy B; Tsoh, Janice Y; Humfleet, Gary; Delucchi, Kevin; Rossi, Joseph S; Redding, Colleen A; Eisendrath, Stuart

    2005-04-01

    This study reports on baseline characteristics associated with acceptance and refusal of available smoking treatment among currently depressed smokers in a psychiatric outpatient clinic who were enrolled in a larger clinical trial. The sample (N=154) was 68% female and 72% White, with a mean age of 41.4 years and average smoking rate of 17 cigarettes/day. All participants were assigned to a repeated contact experimental condition; received a stage-based expert system program to facilitate treatment acceptance; and were then offered smoking treatment, consisting of behavioral counseling, nicotine patch, and bupropion. Acceptors (n=53) were defined as those accepting behavioral counseling and pharmacological treatment at some point during the 18-month study, whereas refusers (n=101) received only the expert system. The number of days to treatment acceptance was significantly predicted by stage of change, with those in preparation entering treatment more quickly than contemplators or precontemplators. In a logistic regression, the variables most strongly associated with accepting treatment were current use of psychiatric medication and perceived success for quitting. Severity of depressive symptoms, duration of depression history, and history of recurrent depression were not related to treatment acceptance. Findings have implications for the psychiatric assessment and treatment of smokers in clinical settings. Psychiatric medication may play a significant role in smoking cessation treatment acceptance by currently depressed smokers. PMID:16036278

  17. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    PubMed

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.

  18. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    PubMed

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content. PMID:27287270

  19. The influence of occupational stress factors on nicotine dependence among students of health and nonhealth care professional colleges

    PubMed Central

    Chopra, Amandeep; Lakhanpal, Manav; Gupta, Nidhi; Suri, Varun; Kaur, Gurwant; Bhudhiraja, Swati

    2015-01-01

    Objectives: To study the relationship between perceived job stress measured using Effort-Reward Imbalance (ERI) scale and nicotine dependence using Fagerström Test for Nicotine Dependence (FTND) scale among students of health and nonhealth care professional colleges. Materials and Methods: A descriptive cross-sectional study was carried on convenient sample of 408 health and nonhealth care professional who were current smokers. Nicotine dependence was measured using the FTND. The extent of the stress factors experienced at work was assessed using the ERI. Chi-square test and logistic regression were used for the statistical analysis. Results: Occupational stress factors are actually associated with higher levels of nicotine dependence (odds ratio = 4.523). The degree of nicotine dependence and stress imbalance was found to be more among health care professional students as compared to nonhealth care professional students (P < 0.05). Being religious was found to have a significant effect in reducing nicotine dependence. Conclusion: Being religious, having low occupational stress and being nonhealth care professional have a significant effect on the prevention of nicotine dependence. PMID:26778887

  20. Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

    PubMed Central

    Li-Sha, Ge; Jing-Lin, Zhao; Guang-Yi, Chen; Li, Liu; De-Pu, Zhou; Yue-Chun, Li

    2015-01-01

    The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis. PMID:26507386

  1. Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3.

    PubMed

    Li-Sha, Ge; Jing-Lin, Zhao; Guang-Yi, Chen; Li, Liu; De-Pu, Zhou; Yue-Chun, Li

    2015-10-28

    The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.

  2. Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence.

    PubMed

    Wu, Jie; Gao, Ming; Taylor, Devin H

    2014-03-01

    Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosable alcohol use disorders. Alcohol is currently responsible for the death of 4% of adults worldwide (about 2.5 million deaths each year), and this number will be significantly increased by 2020 unless effective action is taken. Alcohol is the most commonly abused substance by humans. Ethanol (EtOH) is the intoxicating agent in alcoholic drinks that can lead to abuse and dependence. Although it has been extensively studied, the mechanisms of alcohol reward and dependence are still poorly understood. The major reason is that, unlike other addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular targets, EtOH affects much wider neuronal functions. These functions include phospholipid membranes, various ion channels and receptors, synaptic and network functions, and intracellular signaling molecules. The major targets in the brain that mediate EtOH's effects remain unclear. This knowledge gap results in a therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and nicotine are often co-abused, which suggests that neuronal nicotinic acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also contribute to alcohol's abusive properties. Here, we briefly summarize recent lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway, which provides a perspective that nAChRs are important targets mediating alcohol abuse.

  3. Time dependency of craving and response inhibition during nicotine abstinence

    PubMed Central

    Tsaur, Stephen; Strasser, Andrew A.; Souprountchouk, Valentina; Evans, Gretchen C.; Ashare, Rebecca L.

    2015-01-01

    Background Nicotine withdrawal produces increased craving for cigarettes and deficits in response inhibition, and these withdrawal symptoms are predictive of relapse. Although it is well-established that these symptoms emerge early during abstinence, there is mixed evidence regarding whether they occur simultaneously. Given the importance of the early withdrawal period, this study examined craving and response inhibition at 24h and 72h abstinence. Methods Twenty-one non-treatment seeking adult smokers were evaluated at baseline, 24h, and 72h abstinence for craving (Questionnaire on Smoking Urges – Brief) and response inhibition (Stop Signal Task, Stroop Task, Continuous Performance Task). Generalized linear regression models were used for primary outcomes, and Pearson correlations for examining the association between craving and response inhibition. Results Factor 2 craving (anticipated relief of negative affect) increased from baseline to 24h abstinent (p=0.004), which subsided by 72h (p=0.08). Deficits in response inhibition measured by the Stop Signal Task were observed at 72h (p=0.046), but not 24h (p=0.318). No correlation was found between response inhibition and craving at any time point (p-values>0.19), except between the Stroop Task and factor 1 craving at baseline (p=0.025). Conclusions Factor 2 craving peaked at 24h, whereas deficits in response inhibition did not emerge until 72h, indicating that need to target craving and cognitive function during early abstinence may not occur simultaneously. Further characterizing the time course of withdrawal symptoms may guide development of targeted treatments for smoking cessation. PMID:26052265

  4. [Development of physical dependence on nicotine and endogenous opioid system--participation of α7 nicotinic acetylcholine receptor].

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro; Yamamoto, Chizuko

    2014-10-01

    Nicotine (NIC) regulates various cellular functions acting on the nicotinic acetylcholine receptor (nAChR). And nAChR consists of ligand-gated cation channels with pentameric structure and composed of α and β subunits. In the central nervous system, α 4 β 2 and α 7 nAChRs are the most abundantly expressed as nAChR subtypes. There are several lines of evidence indicating that systemic administration of NIC elicits the release of endogenous opioids, such as, endorphins, enkephalins and dynorphins, in the brain. NIC exerts numerous acute effects, for example, antinociceptive effects and the activating effects of the hypothalamic-pituitary-adrenal (HPA) axis. In these effects, NIC-induced antinociception, but not HPA axis activation, was inhibited by opioid receptor antagonist, naloxone (NLX), and was also suppressed in morphine tolerated mice, indicating the participation of the endogenous opioid system in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception was antagonized by both α 4 β 2 and α 7 nAChR antagonists, while NIC-induced HPA axis activation was antagonized by α 4 β 2 nAChR antagonist, but not by α 7 nAChR antagonist. These results suggest that the endogenous opioid system may not be located on the downstream of α 4 β 2 nAChR. On the other hand, NIC has substantial physical dependence liability. NLX elicits NIC withdrawal after repeated NIC administration evaluated by corticosterone increase as a withdrawal sign, and NLX-precipitated NIC withdrawal is inhibited by concomitant administration of other opioid receptor antagonist, naltrexone, indicating the participation of endogenous opioid system in the development of physical dependence on NIC. NLX-precipitated NIC withdrawal was also inhibited by concomitant administration of an α 7 nAChR antagonist, but not an α 4 β 2 nAChR antagonist. Taken together, these findings suggest that the endogenous opioid system may be located on the downstream of α 7

  5. [Development of physical dependence on nicotine and endogenous opioid system--participation of α7 nicotinic acetylcholine receptor].

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro; Yamamoto, Chizuko

    2014-10-01

    Nicotine (NIC) regulates various cellular functions acting on the nicotinic acetylcholine receptor (nAChR). And nAChR consists of ligand-gated cation channels with pentameric structure and composed of α and β subunits. In the central nervous system, α 4 β 2 and α 7 nAChRs are the most abundantly expressed as nAChR subtypes. There are several lines of evidence indicating that systemic administration of NIC elicits the release of endogenous opioids, such as, endorphins, enkephalins and dynorphins, in the brain. NIC exerts numerous acute effects, for example, antinociceptive effects and the activating effects of the hypothalamic-pituitary-adrenal (HPA) axis. In these effects, NIC-induced antinociception, but not HPA axis activation, was inhibited by opioid receptor antagonist, naloxone (NLX), and was also suppressed in morphine tolerated mice, indicating the participation of the endogenous opioid system in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception was antagonized by both α 4 β 2 and α 7 nAChR antagonists, while NIC-induced HPA axis activation was antagonized by α 4 β 2 nAChR antagonist, but not by α 7 nAChR antagonist. These results suggest that the endogenous opioid system may not be located on the downstream of α 4 β 2 nAChR. On the other hand, NIC has substantial physical dependence liability. NLX elicits NIC withdrawal after repeated NIC administration evaluated by corticosterone increase as a withdrawal sign, and NLX-precipitated NIC withdrawal is inhibited by concomitant administration of other opioid receptor antagonist, naltrexone, indicating the participation of endogenous opioid system in the development of physical dependence on NIC. NLX-precipitated NIC withdrawal was also inhibited by concomitant administration of an α 7 nAChR antagonist, but not an α 4 β 2 nAChR antagonist. Taken together, these findings suggest that the endogenous opioid system may be located on the downstream of α 7

  6. Comparisons of three nicotine dependence scales in a multiethnic sample of young adult menthol and non-menthol smokers

    PubMed Central

    Fagan, Pebbles; Pohkrel, Pallav; Herzog, Thaddeus; Pagano, Ian; Vallone, Donna; Trinidad, Dennis R.; Sakuma, Kari-Lyn; Sterling, Kymberle; Fryer, Craig S.; Moolchan, Eric

    2016-01-01

    Background Few studies have compared nicotine dependence among menthol and non-menthol cigarette smokers in a multiethnic sample of young adult daily cigarette smokers. This study examines differences in nicotine dependence among menthol and non-menthol daily smokers and the associations of nicotine dependence with quitting behaviors among Native Hawaiian, Filipino, and White cigarette smokers aged 18–35. Methods Craigslist.org, newspaper advertisements, and peer-to-peer referrals were used to recruit daily smokers (n = 186) into a lab-based study. Nicotine dependence was assessed using the Fagerstrom Test of Nicotine Dependence (FTND), the Nicotine Dependence Syndrome Scale (NDSS), and the brief Wisconsin Inventory for Smoking Dependence Motives (WISDM). Multiple regression analyses were used to examine differences in nicotine dependence between menthol and non-menthol smokers and the relationship between each nicotine dependence scale with self-efficacy to quit, quit attempt in the past 12 months, and number of attempts. Results Menthol smokers were more likely to report difficulty refraining from smoking in places where forbidden (p = .04) and had higher scores on social/environmental goads subscale of the WISDM (p = . 0005). Two-way interaction models of the FTND and menthol status showed that menthol smokers with higher levels of dependence were more likely to have tried to quit smoking in the past 12 months (p = .02), but were less likely to have had multiple quit attempts (p =.01). Conclusions Components of the FTND and WISDM distinguish levels of dependence between menthol and non-menthol smokers. Higher FTND scores were associated with having a quit attempt, but fewer quit attempts among menthol smokers. PMID:25744873

  7. Relationship between PTSD symptomatology and nicotine dependence severity in crime victims.

    PubMed

    Baschnagel, Joseph S; Coffey, Scott F; Schumacher, Julie A; Drobes, David J; Saladin, Michael E

    2008-11-01

    Smoking rates are higher and cessation rates are lower among individuals with posttraumatic stress disorder (PTSD) compared to the general population, thus understanding the relationship between PTSD and nicotine dependence is important. In a sample of 213 participants with a crime-related trauma (109 with PTSD), the relationship between PTSD status, smoking status (smoker vs. non-smoker), substance abuse diagnosis (SUD), PTSD symptoms, and sex was assessed. SUD diagnosis was significantly related to smoking status, but PTSD symptomatology and sex were not. Among smokers (n=117), increased nicotine dependence severity was associated with being male and with increased level of PTSD avoidance symptoms. Correlations indicated that PTSD avoidance and hyperarousal symptom clusters and total PTSD symptom scores were significantly related to nicotine dependence severity in males, while PTSD symptomatology in general did not correlate with dependence severity for females. The results suggest that level of PTSD symptomatology, particularly avoidance symptoms, may be important targets for smoking cessation treatment among male smokers who have experienced a traumatic event.

  8. Nicotine self-administration induces CB1-dependent LTP in the bed nucleus of the stria terminalis.

    PubMed

    Reisiger, Anne-Ruth; Kaufling, Jennifer; Manzoni, Olivier; Cador, Martine; Georges, François; Caillé, Stephanie

    2014-03-19

    Nicotine addiction is characterized by repetitive drug taking and drug seeking, both tightly controlled by cannabinoid CB1 receptors. The responsiveness of neurons of the bed nucleus of the stria terminalis (BNST) to infralimbic cortex (ILCx) excitatory inputs is increased in rats with active, but not passive, nicotine taking. Therefore, we hypothesize that acquisition of the learned association between nicotine infusion and a paired cue light permits the strengthening of the ILCx-BNST synapses after ILCx tetanic stimulation. We exposed rats to intravenous nicotine self-administration for 2 months. Using a combination of in vivo protocols (electrical stimulations, extracellular recordings, and pharmacological manipulations), we characterized the effects of 10 Hz stimulation of the ILCx on BNST excitatory responses, under different conditions of exposure to nicotine. In addition, we tested whether the effects of the stimulation were CB1 receptor-dependent. The results show that nicotine self-administration supports the induction of evoked spike potentiation in the BNST in response to 10 Hz stimulation of ILCx afferents. Although not altered by nicotine abstinence, this cellular adaptation was blocked by CB1 receptor antagonism. Moreover, blockade of BNST CB1 receptors prevented increases in time-out responding subsequent to ILCx stimulation and decreased cue-induced reinstatement. Thus, the synaptic potentiation within the BNST in response to ILCx stimulation seems to contribute to the cue-elicited responding associated with nicotine self-administration and is tightly controlled by CB1 receptors.

  9. Influence of Smoking Consumption and Nicotine Dependence Degree in Cardiac Autonomic Modulation

    PubMed Central

    dos Santos, Ana Paula Soares; Ramos, Dionei; de Oliveira, Gabriela Martins; dos Santos, Ana Alice Soares; Freire, Ana Paula Coelho Figueira; It, Juliana Tiyaki; Fernandes, Renato Peretti Prieto; Vanderlei, Luiz Carlos Marques; Ramos, Ercy Mara Cipulo

    2016-01-01

    Background Smoking consumption alters cardiac autonomic function. Objective Assess the influence of the intensity of smoking and the nicotine dependence degree in cardiac autonomic modulation evaluated through index of heart rate variability (HRV). Methods 83 smokers, of both genders, between 50 and 70 years of age and with normal lung function were divided according to the intensity of smoking consumption (moderate and severe) and the nicotine dependency degree (mild, moderate and severe). The indexes of HRV were analyzed in rest condition, in linear methods in the time domain (TD), the frequency domain (FD) and through the Poincaré plot. For the comparison of smoking consumption, unpaired t test or Mann-Whitney was employed. For the analysis between the nicotine dependency degrees, we used the One-way ANOVA test, followed by Tukey's post test or Kruskal-Wallis followed by Dunn's test. The significance level was p < 0,05. Results Differences were only found when compared to the different intensities of smoking consumption in the indexes in the FD. LFun (62.89 ± 15.24 vs 75.45 ± 10.28), which corresponds to low frequency spectrum component in normalized units; HFun (37.11 ± 15.24 vs 24.55 ± 10.28), which corresponds to high frequency spectrum component in normalized units and in the LF/HF ratio (2.21 ± 1.47 vs 4.07 ± 2.94). However, in the evaluation of nicotine dependency, significant differences were not observed (p > 0.05). Conclusion Only the intensity of smoking consumption had an influence over the cardiac autonomic modulation of the assessed tobacco smokers. Tobacco smokers with severe intensity of smoking consumption presented a lower autonomic modulation than those with moderate intensity. PMID:27142649

  10. Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers.

    PubMed

    Moran-Santa Maria, Megan M; Hartwell, Karen J; Hanlon, Colleen A; Canterberry, Melanie; Lematty, Todd; Owens, Max; Brady, Kathleen T; George, Mark S

    2015-03-01

    The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z > 2.3, P = 0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r(2)  = 0.15; P < 0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers.

  11. Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers

    PubMed Central

    Cooper, Kim N.; Mahoney, James J.; Bordnick, Patrick S.; Salas, Ramiro; Kosten, Thomas R.; Dani, John A.; De La Garza, Richard

    2015-01-01

    Introduction: Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving. Methods: Nicotine-dependent cigarette smokers were recruited for a 2 day study. On Day 1, participants smoked as usual and on Day 2 were deprived from smoking overnight. On both days, participants completed self-assessment questionnaires on withdrawal, craving, and nicotine-dependence. Participants completed a VR session during the cigarette deprivation condition only (Day 2). During this session, they were exposed to active smoking and placebo (non-smoking) cues. Results: The data show that self-reported levels of “craving” (p < .01) and “thinking about cigarettes” (p < .0001) were significantly greater after exposure to the active cues versus non-smoking cues. Significant increases in heart rate were found for 3 of 4 active cues when compared to non-smoking cues (p < .05). Finally, significant positive correlations were found between self-reported craving prior to the VR session and craving induced by active VR cues (p < .01). Conclusions: In this report, active VR cues elicited craving during cigarette deprivation. This is the first study to demonstrate that self-reported craving, withdrawal symptoms, and nicotine dependence severity predict cue-induced craving in the VR setting. PMID:25475087

  12. Suicidal Behavior in Chemically Dependent Adolescents.

    ERIC Educational Resources Information Center

    Cavaiola, Alan A.; Lavender, Neil

    1999-01-01

    Study explores distinctions between chemically dependent suicide attempters, chemically dependent nonsuicidal adolescents, and high school students with no history of chemical dependency (N=250). Results reveal that there were significant differences between the chemically dependent groups. It was also found that the majority of suicidal gestures…

  13. Does Tramadol Increase the Severity of Nicotine Dependence? A Study in an Egyptian Sample.

    PubMed

    Shalaby, Amr Said; El-Hady Sweilum, Ola Abd; Ads, Mahmoud Khalid

    2015-01-01

    In Egypt, tramadol abuse is increasing, especially among youths and the middle- aged. Tobacco smoking is a worldwide health problem responsible for more deaths and disease than any other noninfectious cause. To investigate if there is a relationship between tramadol and nicotine dependence. 48 tramadol addicts completed a demographic sheet, drug use questionnaire, and the Fagerstrom Test for Nicotine Dependence (FTND). Numbers of cigarettes smoked were recorded every week or two weeks at follow-up or by phone calls, and the FTND was completed again five weeks after abstinence. All participants underwent full psychiatric assessment, plus a urine toxicology screening at first visit, and once again during follow-ups. All subjects of the study were cigarette smokers. The mean numbers of cigarettes smoked per day were 13, 31.8, 20.2, and 14.3 during the phase before tramadol taking, addiction phase, two weeks and five weeks after stopping tramadol. The mean FTND score dropped from 6.67 during the tramadol addiction phase to 4.31 only five weeks after stopping tramadol. Tramadol increases the severity of nicotine dependence. The relation seems to be bi-directional, so increased cigarette smoking also increases tramadol intake.

  14. Effects of chronic nicotine treatment on expression of diverse nicotinic acetylcholine receptor subtypes. I. Dose- and time-dependent effects of nicotine treatment.

    PubMed

    Ke, L; Eisenhour, C M; Bencherif, M; Lukas, R J

    1998-08-01

    Nicotinic acetylcholine receptors (nAChRs) exist as a diverse family of physiologically important ligand-gated ion channels active in classic, excitatory neurotransmission and perhaps in more novel forms of neurochemical signaling. Because of their critical functional roles centrally and peripherally, nAChRs are ideal targets for the regulation of nervous system function. nAChRs also are targets of nicotine, which acts acutely like acetylcholine to stimulate nAChR function. Here, we report studies using model cell culture systems testing the general hypothesis that more chronic nicotine exposure has unique effects on nAChRs. Chronic nicotine treatment induces increases in numbers of human muscle-type nAChRs containing alpha-1, beta-1, gamma and delta subunits, a human ganglionic nAChR subtype containing alpha-3 and beta-4 subunits and a human ganglionic nAChR containing alpha-7 subunits in intracellular and (except for alpha-7 nAChRs) in cell surface pools. However, the half-maximal potency with which nicotine has these effects differs across these nAChR subtypes, as do rates and magnitudes of the "nicotine-induced nAChR up-regulation." These changes in nAChR numbers are not attributable to either transient or sustained changes in nAChR subunit mRNA levels. Nicotine exposure more potently, more rapidly, and with nAChR-subtype specificity, induces two phases of losses in functional responsiveness of muscle-type nAChRs and alpha-3 beta-4 nAChRs, including a "persistent inactivation" that is distinct from classicly defined "desensitization." Based on these results, we hypothesize that chronic nicotine treatment induces persistent functional inactivation and numerical up-regulation of all nAChR subtypes via distinct post-transcriptional mechanisms and with potencies, at rates and with magnitudes that are nAChR-subtype specific. We also hypothesize that chronic nicotine exposure produces long-lasting changes in nervous system function, at least in part, by disabling

  15. Paradise Lost: The relationships between neurological and psychological changes in nicotine-dependent patients

    PubMed Central

    Isomura, Takeshi; Suzuki, Joji; Murai, Toshiya

    2014-01-01

    The neural reward circuit and cognitive distortion play an important role in addiction; however, the relationship between the two has not yet been addressed. In this article, we review recent findings on nicotine dependence and propose a novel hypothesis. Previous research using functional magnetic resonance imaging (fMRI) has shown that while activation of the reward circuit (ventral striatum) appears in response to tobacco-related rewards in nicotine dependence, responses to rewards other than tobacco (e.g. food and money) are reduced. Moreover, this change is observed at the very early stages of smoking, even when a person has smoked fewer than 10 cigarettes in his/her lifetime. Thus, we propose the following hypothesis, called the Paradise Lost theory: given addicts’ lower ventral striatal responses to non-tobacco rewards, nicotine addiction disables smokers from sensing the pleasures of ordinary life (the Paradise Lost state). However, since smokers do not notice this, they produce an overestimation of tobacco (cognitive distortion), such that they do not have many pastimes other than smoking or feel that quitting smoking would reduce the happiness and pleasure and increase the difficulty of life. Cognitive distortion thus makes it difficult for smokers to take the initiative to quit smoking and even causes relapse after smoking cessation. This theory furthers our understanding of addiction and could improve our approach to the prevention and treatment of addiction. PMID:24719610

  16. d-Cycloserine Attenuates Reactivity to Smoking Cues in Nicotine Dependent Smokers: A Pilot Investigation

    PubMed Central

    Santa Ana, Elizabeth J.; Rounsaville, Bruce J.; Frankforter, Tami L.; Nich, Charla; Babuscio, Theresa; Poling, James; Gonsai, Kishorchandra; Hill, Kevin P.; Carroll, Kathleen M.

    2009-01-01

    Increasing evidence indicates that smoking cues contribute to nicotine self-administration and attenuating conditioned reactivity to smoking cues may aid abstinence of smoking and prevention of smoking relapse in individuals with nicotine dependence. Based on prior studies showing that the partial N-methyl-d-aspartate (NMDA) agonist d-cycloserine (DCS) facilitates extinction of learned fear during behavioral exposure therapy in humans and facilitates extinction of cocaine-induced conditioned place preference in animals, we evaluated whether DCS would have potential for reducing reactivity to smoking cues when combined with cue exposure treatment in humans with nicotine dependence. In this double-blind placebo controlled pilot laboratory study, twenty-five smokers were recruited from the general community and randomized to DCS or placebo, plus cue exposure therapy. DCS significantly attenuated smoking cue reactivity in response to in-vivo smoking cues based on physiological reactivity and subjective urge-to-smoke ratings and led to a significantly smaller expired carbon monoxide (CO) level at the 1-week follow-up compared to placebo, although exploratory analyses indicated no effect on smoking behavior overall. These findings provide promising support for DCS combined with cue exposure therapy in attenuating conditioned reactivity to smoking cues. PMID:19592176

  17. Gestational nicotine exposure modifies myelin gene expression in the brains of adolescent rats with sex differences.

    PubMed

    Cao, J; Wang, J; Dwyer, J B; Gautier, N M; Wang, S; Leslie, F M; Li, M D

    2013-04-16

    Myelination defects in the central nervous system (CNS) are associated with various psychiatric disorders, including drug addiction. As these disorders are often observed in individuals prenatally exposed to cigarette smoking, we tested the hypothesis that such exposure impairs central myelination in adolescence, an important period of brain development and the peak age of onset of psychiatric disorders. Pregnant Sprague Dawley rats were treated with nicotine (3 mg kg(-1) per day; gestational nicotine (GN)) or gestational saline via osmotic mini pumps from gestational days 4-18. Both male and female offsprings were killed on postnatal day 35 or 36, and three limbic brain regions, the prefrontal cortex (PFC), caudate putamen and nucleus accumbens, were removed for measurement of gene expression and determination of morphological changes using quantitative real-time PCR (qRT-PCR) array, western blotting and immunohistochemical staining. GN altered myelin gene expression at both the mRNA and protein levels, with striking sex differences. Aberrant expression of myelin-related transcription and trophic factors was seen in GN animals, which correlated highly with the alterations in the myelin gene expression. These correlations suggest that these factors contribute to GN-induced alterations in myelin gene expression and also indicate abnormal function of oligodendrocytes (OLGs), the myelin-producing cells in the CNS. It is unlikely that these changes are attributable solely to an alteration in the number of OLGs, as the cell number was changed only in the PFC of GN males. Together, our findings suggest that abnormal brain myelination underlies various psychiatric disorders and drug abuse associated with prenatal exposure to cigarette smoke.

  18. Calcium/calmodulin-dependent protein kinase IV mediates acute nicotine-induced antinociception in acute thermal pain tests

    PubMed Central

    Jackson, Kia J.; Damaj, M. Imad

    2014-01-01

    Calcium activated second messengers such as calcium/calmodulin-dependent protein kinase II have been implicated in drug-induced antinociception. The less abundant calcium activated second messenger, calcium/calmodulin-dependent protein kinase IV (CaMKIV), mediates emotional responses to pain and tolerance to morphine analgesia; however its role in nicotine-mediated antinociception is currently unknown. The goal of this study was to evaluate the role of CaMKIV in the acute effects of nicotine, primarily acute nicotine- induced antinociception. CaMKIV knockout (−/−), heterozygote (+/−), and wild-type (+/+) mice were injected with various doses of nicotine and evaluated in a battery of tests, including the tail-flick and hot-plate tests for antinociception, body temperature, and locomotor activity. Our results show a genotype-dependent reduction in tail-flick and hot- plate latency in CaMKIV (+/−) and (−/−) mice after acute nicotine treatment, while no difference was observed between genotypes in the body temperature and locomotor activity assessments. The results of this study support a role for CaMKIV in acute nicotine-induced spinal and supraspinal pain mechanisms, and further implicate involvement of calcium-dependent mechanisms in drug-induced antinociception. PMID:24196027

  19. A Feasibility Study of Virtual Reality-Based Coping Skills Training for Nicotine Dependence

    PubMed Central

    Bordnick, Patrick S.; Traylor, Amy C.; Carter, Brian L.; Graap, Ken M.

    2014-01-01

    Objective Virtual reality (VR)-based cue reactivity has been successfully used for the assessment of drug craving. Going beyond assessment of cue reactivity, a novel VR-based treatment approach for smoking cessation was developed and tested for feasibility. Method In a randomized experiment, 10-week treatment feasibility trial, 46 nicotine-dependent adults, completed the10-week program. Virtual reality skills training (VRST) combined with nicotine replacement therapy (NRT) was compared to NRT alone. Participants were assessed for smoking behavior and coping skills during, at end of treatment, and at posttreatment follow-up. Results Smoking rates and craving for nicotine were significantly lower for the VRST group compared to NRT-only group at the end of treatment. Self-confidence and coping skills were also significantly higher for the VRST group, and number of cigarettes smoked was significantly lower, compared to the control group at follow-up. Conclusions Feasibility of VRST was supported in the current study. PMID:25484549

  20. A Comparison of Trauma Profiles among Individuals with Prescription Opioid, Nicotine or Cocaine Dependence

    PubMed Central

    Lawson, Katie M.; Back, Sudie E.; Hartwell, Karen J.; Maria, Megan Moran-Santa; Brady, Kathleen T.

    2013-01-01

    Exposure to traumatic events is common among individuals with substance use disorders. Little is known, however, about the trauma histories among individuals with various types of addiction. The present study compared the trauma histories (general, sexual, physical and emotional) of non-treatment seeking outpatients dependent on prescription opioids (n=41), nicotine (n=87) or cocaine (n=73). The Life Stressor Checklist-Revised (LSC-R) was completed by participants to assess childhood and adult trauma. The findings revealed that all three groups endorsed high levels of trauma exposure, with 96.5% of the entire sample experiencing at least one traumatic event in their lifetime. The prescription opiate group experienced a greater number of general and total traumas than the nicotine group. However, no group differences in the number of emotional, physical, or sexual traumas were revealed. The prescription opiate group reported a younger age of first traumatic event than the cocaine group, and was significantly more likely to report childhood traumatic events than both the cocaine and nicotine groups. The findings provide clinically relevant information that may help improve screening, interventions, and preventative efforts. PMID:23414497

  1. Sodium-dependent inhibition by PN200-110 enantiomers of nicotinic adrenal catecholamine release.

    PubMed Central

    Cárdenas, A. M.; Montiel, C.; Artalejo, A. R.; Sánchez-García, P.; García, A. G.

    1988-01-01

    1. Dimethylphenylpiperazinium (DMPP) or high K concentrations evoke catecholamine release from perfused cat adrenal glands; in both cases the secretory response was significantly enhanced in the absence of Na. Tetrodotoxin did not modify the nicotinic secretory response. 2. The (+)- and (-)-enantiomers of the dihydropyridine Ca channel blocker PN200-110 show a high degree of stereoselectivity in the inhibition of catecholamine secretion evoked by high K or by DMPP in the presence of Na, the (+)-enantiomer being 57 and 80 times more potent, respectively, than the (-)-enantiomer. Both, noradrenaline and adrenaline release were equally depressed by PN200-110. 3. The IC50 values for (+)- and (-)-PN200-110 for blockade of the secretory response induced by K or DMPP in the presence of Na are in the same range. In the absence of Na, (-)-PN200-110 did not affect DMPP-evoked secretion; however, the (+)-enantiomer partially inhibited it. 4. The results suggest that the physiological catecholamine release from chromaffin cells is preceded by Na entry through the nicotinic receptor-associated ionophore; this causes cell depolarization, opening of voltage-dependent, dihydropyridine-sensitive Ca channels and Ca entry into the cell. In the absence of Na, additional Ca influx through an alternative pathway (the nicotinic cholinoceptor ionophore?) might also activate secretion. PMID:2975522

  2. Role of the D3 dopamine receptor in nicotine sensitization.

    PubMed

    Smith, Laura N; Bachus, Susan E; McDonald, Craig G; Smith, Robert F

    2015-08-01

    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.

  3. Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers

    PubMed Central

    Hartwell, Karen J.; Hanlon, Colleen A.; Li, Xingbao; Borckardt, Jeffrey J.; Canterberry, Melanie; Prisciandaro, James J.; Moran-Santa Maria, Megan M.; LeMatty, Todd; George, Mark S.; Brady, Kathleen T.

    2016-01-01

    Background Cue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers. Methods Nicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided. Results Forty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group. Limitations As participants were not seeking treatment, clinical outcomes are lacking. Conclusion Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue–elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality. PMID:26505139

  4. Nicotine Dependence as a Mediator of Project EX’s Effects to Reduce Tobacco Use in Scholars

    PubMed Central

    Gonzálvez, María T.; Espada, José P.; Orgilés, Mireia; Morales, Alexandra; Sussman, Steve

    2016-01-01

    In Spain, 44% of 14–18-year-olds have smoked, and 12.5% have smoked cigarettes in the last 30 days. Nicotine is one of the most addictive substances, and can lead to serious addiction in adulthood with adverse consequences to one’s health. School plays a relevant role in health promotion and preventing risk behaviors such as tobacco consumption. Despite the fact that some school-based tobacco cessation and prevention interventions prove to be effective for their purposes, there is a lack of understanding as to why these programs succeed or fail. This longitudinal study aims to test the nicotine dependence (ND) as a mediator of Project EX’s effect – a tobacco-use cessation program developed for high school youth to reduce tobacco consumption in scholars. Six high schools located in the Mediterranean coast were randomized for the participation of the program (Spanish version of Project EX) or a waiting-list group with baseline, immediate-posttest, and 12-month follow-up assessments. At baseline, 1,546 adolescents aged 14–21 years old (mean age: 15.28; SD = 1.20; 46% were women) were evaluated by self-administered tests on tobacco consumption and ND. A biomarker of smoke inhalation – a measurement of exhaled carbon monoxide (ECM) – was used. Participants who were smokers (N = 501; 32%) were selected for this study. Mediation analyses were conducted using the PROCESS v2.12 macro for Windows. The significant criterion was p ≤ 0.05, and 5,000 samples were used for bias-corrected bootstrap confidence intervals. Results indicated that Project EX indirectly decreased the number of cigarettes smoked in the last month, the number of cigarettes smoked within the last 7 days, the number of daily cigarettes, and ECM level at 12-month follow up through decreasing the level of ND in the short-term. This is the first Spanish study that explores ND as a mediator of the long-term efficacy of Project EX to reduce tobacco consumption in adolescents. Results suggest that

  5. ADHD in adolescence and adulthood, with a special focus on the dopamine transporter and nicotine

    PubMed Central

    Krause, Johanna; Krause, Klaus-Henning; Dresel, Stefan H.; la Fougère, Christian; Ackenheil, Manfred

    2006-01-01

    The persistence of attention deficit hyperactivity disorder (ADHD) into adolescence and adulthood has now been accepted as a clinical entity. The rate of prevalence among adults is assumed to be from 2% to 4%. With increasing age, a symptom change has to be considered; disturbance of attention becomes more prominent, whereas hyperactivity often diminishes or changes to inactivity. Neuroimaging studies show a high striatal dopamine transporter (DAT) availability in most adults with ADHD; this can be reduced by stimulants. Nicotine seems to have a stimulant-like action on the DAT. In most adults with ADHD, therapy has to be multimodal, combining psychotherapy and medication. Methylphenidate is the first-line drug in adult ADHD; further options are amphetamine and noradrenaline reuptake inhibitors. Nonresponders to methylphenidate seem to have no elevated DAT availability prior to therapy. Combination with other psychiatric disorders occurs frequently in adults with ADHD; in these patients additional pharmacological treatment with special regard to the comorbid disease is recommended. PMID:16640111

  6. [The management of patients with nicotine dependence - the role of the general practitioners].

    PubMed

    Ruff, Paul

    2010-08-01

    The gatekeeper needs a disease management of his patients who smoke. Questionnaires will help to define the diagnosis and grade of nicotine dependence as well as the fingerprint of the patients smoking career. The ICD-10 Code and the Fagerström Nicotine Dependence Test are used. There is no therapy indicated without the optimal motivation of the patient. The transtheoretical model of Prochaska and DiClemente ist widely accepted to separate the stadium of motivation into precontemplation, contemplation, preparation and action. Many other factors like earlier experiences, catastrophe scenaries, self-efficacy and selection of therapeutic modality are important for the best outcome. 90 % of the work of a gatekeeper is minimal intervention. This means individually tailored argumentations to shift the motivation of the patient to smoking cessation. The concept is defined in the rules of the five R's with relevance, risks, rewards, roadblocks and repetition. Following these criterias, the gatekeeper gets a positive shift of his motivation in up to 60 % with only one minimal intervention. The smoking cessation guidelines through the world are very similar and show a level A grade for a synergy of behavioural therapy and medication by either nicotine replacement, bupropion or vareniclin. The selection of any other regimen is either less efficient or anecdotally and leads to a further loss of life expectancy of the smoker. The gatekeeper has the infrastructure, the know how and the confidence of his patient to act as disease manager. A successful therapy is possible over six months with about seven consultations, the success rate is expected to be even higher than the values in the medication studies. Smokers should be informed by the health organizations to avoid self therapies and look for specialists help. The gatekeeper is an ideal candidate.

  7. Design Considerations for Smoking Cessation Apps: Feedback From Nicotine Dependence Treatment Providers and Smokers

    PubMed Central

    Hartzler, Andrea L; Catz, Sheryl L

    2016-01-01

    Background Hundreds of smoking cessation apps are commercially available, but most are not theory-based or designed to take advantage of mobile technology in ways that could make them more engaging and possibly more effective. Considering input from both clinical experts (who understand best practice nicotine dependence treatment requirements) to inform appropriate content and from smokers (the end users) to express their preferences is important in designing these programs in the future. Objective To assess and compare the opinions of nicotine dependence treatment providers and smokers regarding the design of future smoking cessation apps. Methods We surveyed providers (n=264) and smokers who own smartphones (n=40) to assess their opinions on the importance of 21 app design features. Features represented 5 domains: cost, reputation, privacy and security, content and user experience, and communication. Domains were chosen to reflect best practice treatment, leverage mobile technology to support smoking cessation, and elicit important user preferences. Data were collected between June and July 2015. Results Most providers agreed that mHealth apps hold promise for helping people quit smoking (203/264, 76.9%) and would recommend them to their clients/patients (201/264, 76.1%), especially if the app were empirically validated (236/264, 89.4%). Few providers believe effective cessation apps currently exist (112/264, 42.4%). Few smokers (5/40, 13%) had ever downloaded a smoking cessation app; of the ones who had not, most said they would consider doing so (29/35, 83%). Both respondent groups indicated the following features were very to extremely important to include in cessation apps: free or low cost, keeps information private, matches individual needs and interests, adapts as one’s needs and interests change, helps to manage nicotine withdrawal symptoms and medication side effects, and allows users to track their progress. Providers and smokers also indicated gaming

  8. The acute effects of nicotine on the subjective and behavioural responses to denicotinized tobacco in dependent smokers.

    PubMed

    Barrett, Sean P; Darredeau, Christine

    2012-06-01

    Both nicotine and various non-nicotine smoking factors are believed to contribute to tobacco addiction but their relative roles remain incompletely understood. This study aimed to help clarify these roles by examining acute interactions between nicotine and denicotinized tobacco (DT). During two randomized blinded sessions, the effects of a quick-release 4 mg nicotine lozenge (NL) versus placebo lozenge (PL) on the subjective and behavioural responses to DT were examined in 27 (14 men) dependent, daily smokers. Participants were administered NL or PL for 30 min before receiving one initial DT cigarette. Participants could then earn additional DT cigarette puffs over the following 60 min. Subjective state was assessed using the Questionnaire of Smoking Urges-Brief and visual analogue scales at baseline, postlozenge and postinitial DT cigarette. Relative to PL, NL was associated with increased alertness as well as with reduced levels of DT self-administration (P<0.01). The administration of a single DT cigarette was followed by a reduction in craving under both lozenge conditions (P<0.001), an effect that was significantly greater in women (P<0.01). Moreover, DT administration was associated with increased ratings of 'pleasant', 'satisfied', 'stimulated' and 'relaxed', as well as with decreased ratings of 'anxious' (P's<0.01), independent of lozenge condition. The findings suggest that both nicotine and non-nicotine smoking factors may make important contributions towards the addictive properties of tobacco. PMID:22470104

  9. Association Between CHRNA3 and CHRNA5 Nicotine Receptor Subunit Gene Variants and Nicotine Dependence in an Isolated Populationof Kashubians in Poland.

    PubMed

    Kita-Milczarska, Karolina; Sieminska, Alicja; Jassem, Ewa

    2016-01-01

    BACKGROUND Genome-wide and allelic association studies have shown the contribution of CHRNA5-A3-B4 nicotinic receptor subunit gene cluster within chromosome 15 to nicotine dependence (ND). While an association between several single-nucleotide polymorphisms (SNPs) at that locus and smoking quantity (cigarettes per day; CPD) has been well recognized, there are some inconsistencies in demonstrating the influence of these SNPs on other ND phenotypes. This uncertainty motivated us to examine the association of 3 selected SNPs (CHRNA3 rs1051730, rs6495308, and CHRNA5 rs55853898) with ND in an isolated population of Kashubians from Poland. MATERIAL AND METHODS The study sample consisted of 788 current daily smokers. ND was assessed by CPD, the Fagerstrom Test for Nicotine Dependence (FTND), its brief version - Heavy Smoking Index (HSI), and time to first cigarette after waking (TTF). The correlation between studied SNPs and dichotomized values of ND measures was assessed in the regression analysis. Bonferroni corrected p-value of 0.017 was set for a type 1 error. RESULTS We found a robust association between risk allele A of rs1051730 and CPD >10 (odds ratio (OR)=1.77, 95% confidence interval (CI): 1.20-2.59, p=0.004), and a weak association, which did not survive correction for multiple testing, with FTND ³4. No associations between studied SNPs and HSI or TTF were demonstrated. CONCLUSIONS Our findings confirm that rs1051730 influences ND phenotype, as defined by CPD. PMID:27127891

  10. Association Between CHRNA3 and CHRNA5 Nicotine Receptor Subunit Gene Variants and Nicotine Dependence in an Isolated Populationof Kashubians in Poland

    PubMed Central

    Kita-Milczarska, Karolina; Sieminska, Alicja; Jassem, Ewa

    2016-01-01

    Background Genome-wide and allelic association studies have shown the contribution of CHRNA5-A3-B4 nicotinic receptor subunit gene cluster within chromosome 15 to nicotine dependence (ND). While an association between several single-nucleotide polymorphisms (SNPs) at that locus and smoking quantity (cigarettes per day; CPD) has been well recognized, there are some inconsistencies in demonstrating the influence of these SNPs on other ND phenotypes. This uncertainty motivated us to examine the association of 3 selected SNPs (CHRNA3 rs1051730, rs6495308, and CHRNA5 rs55853898) with ND in an isolated population of Kashubians from Poland. Material/Methods The study sample consisted of 788 current daily smokers. ND was assessed by CPD, the Fagerstrom Test for Nicotine Dependence (FTND), its brief version - Heavy Smoking Index (HSI), and time to first cigarette after waking (TTF). The correlation between studied SNPs and dichotomized values of ND measures was assessed in the regression analysis. Bonferroni corrected p-value of 0.017 was set for a type 1 error. Results We found a robust association between risk allele A of rs1051730 and CPD >10 (odds ratio (OR)=1.77, 95% confidence interval (CI): 1.20–2.59, p=0.004), and a weak association, which did not survive correction for multiple testing, with FTND ≥4. No associations between studied SNPs and HSI or TTF were demonstrated. Conclusions Our findings confirm that rs1051730 influences ND phenotype, as defined by CPD. PMID:27127891

  11. Incorporating age at onset of smoking into genetic models for nicotine dependence: Evidence for interaction with multiple genes

    PubMed Central

    Grucza, Richard A.; Johnson, Eric O.; Krueger, Robert F.; Breslau, Naomi; Saccone, Nancy L.; Chen, Li-Shiun; Derringer, Jaime; Agrawal, Arpana; Lynskey, Micheal; Bierut, Laura J.

    2011-01-01

    Nicotine dependence is moderately heritable, but identified genetic associations explain only modest portions of this heritability. We analyzed 3,369 SNPs from 349 candidate genes, and investigated whether incorporation of SNP-by-environment interaction into association analyses might bolster gene discovery efforts and prediction of nicotine dependence. Specifically, we incorporated the interaction between allele count and age-at-onset of regular smoking (AOS) into association analyses of nicotine dependence. Subjects were from the Collaborative Genetic Study of Nicotine Dependence, and included 797 cases ascertained for Fagerström nicotine dependence, and 811 non-nicotine dependent smokers as controls, all of European descent. Compared with main-effect models, SNP x AOS interaction models resulted in higher numbers of nominally significant tests, increased predictive utility at individual SNPs, and higher predictive utility in a multi-locus model. Some SNPs previously documented in main-effect analyses exhibited improved fits in the joint-analysis, including rs16969968 from CHRNA5 and rs2314379 from MAP3K4. CHRNA5 exhibited larger effects in later-onset smokers, in contrast with a previous report that suggested the opposite interaction (Weiss et al, PLOS Genetics, 4: e1000125, 2008). However, a number of SNPs that did not emerge in main-effect analyses were among the strongest findings in the interaction analyses. These include SNPs located in GRIN2B (p=1.5 × 10−5), which encodes a subunit of the NMDA receptor channel, a key molecule in mediating age-dependent synaptic plasticity. Incorporation of logically chosen interaction parameters, such as AOS, into genetic models of substance-use disorders may increase the degree of explained phenotypic variation, and constitutes a promising avenue for gene-discovery. PMID:20624154

  12. Measures of Affect and Nicotine Dependence Predict Differential Response to Smoking Cessation Treatments.

    ERIC Educational Resources Information Center

    Zelman, Diane C.; And Others

    1992-01-01

    Randomly assigned smokers (n=126) to six-session smoking cessation treatments consisting of skills training or support counseling strategies and nicotine gum or rapid smoking nicotine exposure strategies. Counseling and nicotine strategies were completely crossed; all four combinations resulted in equivalent one-year abstinence rates. Treatments…

  13. [The prevalence of nicotine-dependency in some populations: a systematic review].

    PubMed

    Campo-Arias, Adalberto

    2006-01-01

    Tobacco use is the leading cause of preventable morbidity-mortality around the world. Nicotine dependence (ND) explains why people continue to smoke even though the harmful outcome associated with tobacco use is well-known. The object of this review was to establish current and one-year prevalence of ND among adults from the general population. Ebsco, Embase, Lilacs, Ovid, Proquest, and PubMed were systematically reviewed. The key words used were: smoking, tobacco, cigarette, nicotine, dependence, adults, general population and cross-sectional study. Only research carried out in English, Portuguese and Spanish was reviewed. A descriptive analysis of six articles was made. Current ND prevalence ranged from 27.8% to 55% (44.7% weighted average) and annual prevalence from 26% to 46.9% (37.7% weighted average). ND was independent of gender and higher amongst heavy smokers. It was concluded that ND prevalence is close to 45% amongst current regular smokers and affected 38% of smokers during the last year. More research is needed. PMID:16703966

  14. Uncovering hidden variance: pair-wise SNP analysis accounts for additional variance in nicotine dependence

    PubMed Central

    Culverhouse, Robert C.; Saccone, Nancy L.; Stitzel, Jerry A.; Wang, Jen C.; Steinbach, Joseph H.; Goate, Alison M.; Schwantes-An, Tae-Hwi; Grucza, Richard A.; Stevens, Victoria L.; Bierut, Laura J.

    2010-01-01

    Results from genome-wide association studies of complex traits account for only a modest proportion of the trait variance predicted to be due to genetics. We hypothesize that joint analysis of polymorphisms may account for more variance. We evaluated this hypothesis on a case–control smoking phenotype by examining pairs of nicotinic receptor single-nucleotide polymorphisms (SNPs) using the Restricted Partition Method (RPM) on data from the Collaborative Genetic Study of Nicotine Dependence (COGEND). We found evidence of joint effects that increase explained variance. Four signals identified in COGEND were testable in independent American Cancer Society (ACS) data, and three of the four signals replicated. Our results highlight two important lessons: joint effects that increase the explained variance are not limited to loci displaying substantial main effects, and joint effects need not display a significant interaction term in a logistic regression model. These results suggest that the joint analyses of variants may indeed account for part of the genetic variance left unexplained by single SNP analyses. Methodologies that limit analyses of joint effects to variants that demonstrate association in single SNP analyses, or require a significant interaction term, will likely miss important joint effects. PMID:21079997

  15. Permanent, sex-selective effects of prenatal or adolescent nicotine exposure, separately or sequentially, in rat brain regions: indices of cholinergic and serotonergic synaptic function, cell signaling, and neural cell number and size at 6 months of age.

    PubMed

    Slotkin, Theodore A; MacKillop, Emiko A; Rudder, Charles L; Ryde, Ian T; Tate, Charlotte A; Seidler, Frederic J

    2007-05-01

    Nicotine is a neuroteratogen that disrupts neurodevelopment and synaptic function, with vulnerability extending into adolescence. We assessed the permanence of effects in rats on indices of neural cell number and size, and on acetylcholine and serotonin (5HT) systems, conducting assessments at 6 months of age, after prenatal nicotine exposure, adolescent exposure, or sequential exposure in both periods. For prenatal nicotine, indices of cell number and size showed few abnormalities by 6 months, but there were persistent deficits in cerebrocortical choline acetyltransferase activity and hemicholinium-3 binding to the presynaptic choline transporter, a pattern consistent with cholinergic hypoactivity; these effects were more prominent in males than females. The expression of 5HT receptors also showed permanent effects in males, with suppression of the 5HT(1A) subtype and upregulation of 5HT(2) receptors. In addition, cell signaling through adenylyl cyclase showed heterologous uncoupling of neurotransmitter responses. Nicotine exposure in adolescence produced lasting effects that were similar to those of prenatal nicotine. However, when animals were exposed to prenatal nicotine and received nicotine subsequently in adolescence, the adverse effects then extended to females, whereas the net effect in males was similar to that of prenatal nicotine by itself. Our results indicate that prenatal or adolescent nicotine exposure evoke permanent changes in synaptic function that transcend the recovery of less-sensitive indices of structural damage; further, prenatal exposure sensitizes females to the subsequent adverse effects of adolescent nicotine, thus creating a population that may be especially vulnerable to the lasting behavioral consequences of nicotine intake in adolescence.

  16. Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.

    PubMed

    Ilott, Nicholas E; Schneider, Tomasz; Mill, Jonathan; Schalkwyk, Leonard; Brolese, Giovana; Bizarro, Lisiane; Stolerman, Ian P; Dempster, Emma; Asherson, Philip

    2014-01-01

    Gestational exposure to environmental toxins such as nicotine may result in detectable gene expression changes in later life. To investigate the direct toxic effects of prenatal nicotine exposure on later brain development, we have used transcriptomic analysis of striatal samples to identify gene expression differences between adolescent Lister Hooded rats exposed to nicotine in utero and controls. Using an additional group of animals matched for the reduced food intake experienced in the nicotine group, we were also able to assess the impact of imposed food-restriction on gene expression profiles. We found little evidence for a role of gestational nicotine exposure on altered gene expression in the striatum of adolescent offspring at a significance level of p<0.01 and |log2 fold change >0.5|, although we cannot exclude the possibility of nicotine-induced changes in other brain regions, or at other time points. We did, however, find marked gene expression differences in response to imposed food-restriction. Food-restriction resulted in significant group differences for a number of immediate early genes (IEGs) including Fos, Fosb, Fosl2, Arc, Junb, Nr4a1 and Nr4a3. These genes are associated with stress response pathways and therefore may reflect long-term effects of nutritional deprivation on the development of the stress system. PMID:24586432

  17. Nicotine dependence and smoking habits in patients with head and neck cancer*

    PubMed Central

    de Almeida, Adriana Ávila; Bandeira, Celso Muller; Gonçalves, Antonio José; Araújo, Alberto José

    2014-01-01

    Objective: To assess smoking habits and nicotine dependence (ND) in patients with head and neck cancer Methods: This study involved 71 smokers or former smokers with squamous cell carcinoma in the oral cavity, pharynx, or larynx who were treated at a university hospital in the city of São Paulo between January and May of 2010. We used the Fagerström Test for Nicotine Dependence to evaluate smoking habits and ND in the sample. Data regarding cancer treatment were collected from medical records. Depending on the variables studied, we used the chi-square test, Fisher's exact test, Student's t-test, or Spearman's correlation test. Results: Of the 71 patients, 47 (66.2%) presented with high or very high ND, 40 (56.3%) smoked more than 20 cigarettes/day, and 32 (45.1%) smoked their first cigarette within 5 min of awakening. Advanced disease stage correlated significantly with the number of cigarettes smoked per day (p = 0.011) and with smoking history (p = 0.047). We found that ND did not correlate significantly with gender, disease stage, smoking cessation, or number of smoking cessation attempts, nor did the number of cigarettes smoked per day correlate with smoking cessation or gender. Treatment for smoking cessation was not routinely offered. Conclusions: In most of the patients studied, the level of ND was high or very high. The prevalence of heavy smoking for long periods was high in our sample. A diagnosis of cancer is a motivating factor for smoking cessation. However, intensive smoking cessation treatment is not routinely offered to smoking patients diagnosed with cancer. PMID:25029652

  18. Possible involvement of endogenous opioid system located downstream of α7 nicotinic acetylcholine receptor in mice with physical dependence on nicotine.

    PubMed

    Ueno, Keiko; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro; Wakida, Naoki; Yamamoto, Chizuko; Maeda, Takehiko; Ozaki, Masanobu; Kishioka, Shiroh

    2014-01-01

    We previously reported that nicotine (NIC)-induced analgesia was elicited in part by activation of the endogenous opioid system. Moreover, it is well known that NIC has physical-dependence liability, but its mechanism is unclear. Therefore, we examined whether physical dependence on NIC was mediated by activation of the endogenous opioid system in ICR mice. We evaluated increased serum corticosterone (SCS) as an indicator of NIC withdrawal, as it is a quantitative indicator of naloxone (opioid receptor antagonist, NLX)-precipitated morphine withdrawal in mice. In this study, NLX precipitated an SCS increase in mice receiving repeated NIC, by a dose-dependent mechanism, and correlated with the dose and number of days of repeated NIC administration. When an opioid receptor antagonist (naltrexone) was concomitantly administered with repeated NIC, the NLX-precipitated SCS increase was not elicited. Concomitant administration of the α7 nicotinic acetylcholine receptor (nAChR) antagonist (methyllycaconitine) with repeated NIC, but not the α4β2 nAChR antagonist (dihydro-β-erythroidine), did not elicit an SCS increase by NLX. Thus, a physical dependence on NIC was in part mediated by the activation of the endogenous opioid system, located downstream of α7 nAChR.

  19. Behavioral, Biochemical, and Molecular Indices of Stress are Enhanced in Female Versus Male Rats Experiencing Nicotine Withdrawal

    PubMed Central

    Torres, Oscar V.; Gentil, Luciana G.; Natividad, Luis A.; Carcoba, Luis M.; O’Dell, Laura E.

    2013-01-01

    Stress is a major factor that promotes tobacco use and relapse during withdrawal. Although women are more vulnerable to tobacco use than men, the manner in which stress contributes to tobacco use in women versus men is unclear. Thus, the goal of this study was to compare behavioral and biological indices of stress in male and female rats during nicotine withdrawal. Since the effects of nicotine withdrawal are age-dependent, this study also included adolescent rats. An initial study was conducted to provide comparable nicotine doses across age and sex during nicotine exposure and withdrawal. Rats received sham surgery or an osmotic pump that delivered nicotine. After 14 days of nicotine, the pumps were removed and controls received a sham surgery. Twenty-four hours later, anxiety-like behavior and plasma corticosterone were assessed. The nucleus accumbens (NAcc), amygdala, and hypothalamus were examined for changes in corticotropin-releasing factor (CRF) gene expression. In order to differentiate the effects of nicotine withdrawal from exposure to nicotine, a cohort of rats did not have their pumps removed. The major finding is that during nicotine withdrawal, adult females display higher levels of anxiety-like behavior, plasma corticosterone, and CRF mRNA expression in the NAcc relative to adult males. However, during nicotine exposure, adult males exhibited higher levels of corticosterone and CRF mRNA in the amygdala relative to females. Adolescents displayed less nicotine withdrawal than adults. Moreover, adolescent males displayed an increase in anxiety-like behavior and an up-regulation of CRF mRNA in the amygdala during nicotine exposure and withdrawal. These findings are likely related to stress produced by the high doses of nicotine that were administered to adolescents to produce equivalent levels of cotinine as adults. In conclusion, these findings suggest that intense stress produced by nicotine withdrawal may contribute to tobacco use in women. PMID

  20. Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain

    PubMed Central

    Webster, J Christopher; Francis, Michael M; Porter, Julia K; Robinson, Gillian; Stokes, Clare; Horenstein, Ben; Papke, Roger L

    1999-01-01

    We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function.The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine.Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage.Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field.An analysis of point mutations indicates that the residues at the 6′ position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10′ position are not sufficient to produce effects, but 6′ 10′ double mutants show more effect than do the 6′ single mutants. PMID:10455283

  1. Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations.

    PubMed

    Abreu-Villaça, Yael; Seidler, Frederic J; Tate, Charlotte A; Slotkin, Theodore A

    2003-07-25

    In the fetus, nicotine is a neuroteratogen that elicits cell damage and loss and subsequent abnormalities of synaptic function. We explored whether these effects extend into adolescence, the period when most people begin smoking. Beginning on postnatal day 30, rats were given a 1 week regimen of nicotine infusions or twice-daily injections, at doses (0.6, 2 and 6 mg/kg/day) set to achieve plasma levels found in occasional to regular smokers. We assessed indices of cell packing density and cell number (DNA concentration and content), cell size (total protein/DNA ratio) and neuritic projections (membrane/total protein) in the midbrain, hippocampus and cerebral cortex, three regions known to be vulnerable to developmental effects of nicotine. With either route of administration, nicotine evoked shortfalls in DNA concentration and content, compensatory elevations of total protein/DNA, and reductions in the membrane/total protein ratio. Nearly all of the effects were apparent even at the lowest dose of nicotine and remained fully evident 1 month posttreatment. Although both males and females showed significant alterations, in general the effects were larger in females. Our results indicate that in adolescence, even a brief period of continuous or intermittent nicotine exposure, elicits lasting alterations in biomarkers associated with cellular and neuritic damage. As the effects are detected at exposures that produce plasma concentrations one-tenth of those in regular smokers, the exquisite sensitivity of the adolescent brain to nicotine neurotoxicity may contribute to lasting neurobehavioral damage even in occasional smokers. PMID:12850578

  2. Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.

    PubMed

    Hancock, D B; Reginsson, G W; Gaddis, N C; Chen, X; Saccone, N L; Lutz, S M; Qaiser, B; Sherva, R; Steinberg, S; Zink, F; Stacey, S N; Glasheen, C; Chen, J; Gu, F; Frederiksen, B N; Loukola, A; Gudbjartsson, D F; Brüske, I; Landi, M T; Bickeböller, H; Madden, P; Farrer, L; Kaprio, J; Kranzler, H R; Gelernter, J; Baker, T B; Kraft, P; Amos, C I; Caporaso, N E; Hokanson, J E; Bierut, L J; Thorgeirsson, T E; Johnson, E O; Stefansson, K

    2015-01-01

    We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerström Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 × 10(-9) across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 × 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences. PMID:26440539

  3. Role of the Neuregulin Signaling Pathway in Nicotine Dependence and Co-morbid Disorders

    PubMed Central

    Fisher, Miranda L.; Loukola, Anu; Kaprio, Jaakko; Turner, Jill R.

    2016-01-01

    Smoking is currently the leading cause of preventable death in the United States and is responsible for over four million deaths annually worldwide. Therefore, there is a vast clinical unmet need with regards to therapeutics targeting smoking cessation. This is even more apparent when examining smokers co-morbid with psychiatric illness, as rates of smoking in this population are ~4× higher than in the general population. Examining common genetic and molecular signaling pathways impinging upon both smoking behavior and psychiatric illness will lead to a better understanding of co-morbid disorders and potential development of novel therapeutics. Studies have implicated the Neuregulin Signaling Pathway in the pathophysiology of a number of psychiatric illnesses. Additionally, recent studies have also shown an association between the Neuregulin Signaling Pathway and smoking behaviors. This review outlines basic mechanisms of the Neuregulin Signaling Pathway and how it may be exploited for precision medicine approaches in treating nicotine dependence and mental illness. PMID:26472527

  4. An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence.

    PubMed

    Frahm, Silke; Antolin-Fontes, Beatriz; Görlich, Andreas; Zander, Johannes-Friedrich; Ahnert-Hilger, Gudrun; Ibañez-Tallon, Ines

    2015-12-01

    A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior.

  5. Role of the Neuregulin Signaling Pathway in Nicotine Dependence and Co-morbid Disorders.

    PubMed

    Fisher, Miranda L; Loukola, Anu; Kaprio, Jaakko; Turner, Jill R

    2015-01-01

    Smoking is currently the leading cause of preventable death in the United States and is responsible for over four million deaths annually worldwide. Therefore, there is a vast clinical unmet need with regards to therapeutics targeting smoking cessation. This is even more apparent when examining smokers co-morbid with psychiatric illness, as rates of smoking in this population are ~4× higher than in the general population. Examining common genetic and molecular signaling pathways impinging upon both smoking behavior and psychiatric illness will lead to a better understanding of co-morbid disorders and potential development of novel therapeutics. Studies have implicated the Neuregulin Signaling Pathway in the pathophysiology of a number of psychiatric illnesses. Additionally, recent studies have also shown an association between the Neuregulin Signaling Pathway and smoking behaviors. This review outlines basic mechanisms of the Neuregulin Signaling Pathway and how it may be exploited for precision medicine approaches in treating nicotine dependence and mental illness. PMID:26472527

  6. Environmental enrichment alters structural plasticity of the adolescent brain but does not remediate the effects of prenatal nicotine exposure.

    PubMed

    Mychasiuk, Richelle; Muhammad, Arif; Kolb, Bryan

    2014-07-01

    Exposure to both drugs of abuse and environmental enrichment (EE) are widely studied experiences that induce large changes in dendritic morphology and synaptic connectivity. As there is an abundance of literature using EE as a treatment strategy for drug addiction, we sought to determine whether EE could remediate the effects of prenatal nicotine (PN) exposure. Using Golgi-Cox staining, we examined eighteen neuroanatomical parameters in four brain regions [medial prefrontal cortex (mPFC), orbital frontal cortex (OFC), nucleus accumben, and Par1] of Long-Evans rats. EE in adolescence dramatically altered structural plasticity in the male and female brain, modifying 60% of parameters investigated. EE normalized three parameters (OFC spine density and dendritic branching and mPFC dendritic branching) in male offspring exposed to nicotine prenatally but did not remediate any measures in female offspring. PN exposure interfered with adolescent EE-induced changes in five neuroanatomical measurements (Par1 spine density and dendritic branching in both male and female offspring, and mPFC spine density in male offspring). And in four neuroanatomical parameters examined, PN exposure and EE combined to produce additive effects [OFC spine density in females and mPFC dendritic length (apical and basilar) and branching in males]. Despite demonstrated efficacy in reversing drug addiction, EE was not able to reverse many of the PN-induced changes in neuronal morphology, indicating that modifications in neural circuitry generated in the prenatal period may be more resistant to change than those generated in the adult brain.

  7. Effects of Intraoperative Dexmedetomidine on Postoperative Pain in Highly Nicotine-Dependent Patients After Thoracic Surgery

    PubMed Central

    Cai, Xingzhi; Zhang, Ping; Lu, Sufen; Zhang, Zongwang; Yu, Ailan; Liu, Donghua; Wu, Shanshan

    2016-01-01

    Abstract To investigate the effects of intraoperative dexmedetomidine on pain in highly nicotine-dependent patients after thoracic surgery. Highly nicotine-dependent men underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia with sufentanil. In dexmedetomidine group (experimental group, n = 46), dexmedetomidine was given at a loading dose of 1 μg/kg for 10 minutes, followed by continuous infusion at 0.5 μg/kg/h until 30 minutes before the end of surgery. The saline group (control group, n = 48) received the same volume of saline. General anesthesia was administered via a combination of inhalation and intravenous anesthetics. If necessary, patients were administered a loading dose of sufentanil by an anesthesiologist immediately after surgery (0 hours). Patient-controlled analgesia was started when the patient's resting numerical rating scale (NRS) score was less than 4. Resting and coughing NRS scores and sufentanil dosage were recorded 0, 1, 4 hours, and every 4 hours until 48 hours after surgery. Dosages of other rescue analgesics were converted to the sufentanil dosage. Surgical data, adverse effects, and degree of satisfaction were obtained. Cumulative sufentanil dosage, resting NRS, and coughing NRS in the first 24 hours after surgery and heart rate were lower in the experimental compared with the control group (P <0.05). No patient experienced sedation or respiratory depression. Frequency of nausea and vomiting and degree of satisfaction were similar in both groups. Intraoperative dexmedetomidine was associated with reduced resting and coughing NRS scores and a sufentanil-sparing effect during the first 24 hours after thoracic surgery. PMID:27258524

  8. Nicotine Modulates Alcohol-Seeking and Relapse by Alcohol-Preferring (P) Rats in a Time Dependent Manner

    PubMed Central

    Hauser, Sheketha R.; Getachew, Bruk; Oster, Scott M.; Dhaher, Ronnie; Ding, Zheng-Ming; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.

    2015-01-01

    Background Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at two different time points. Method Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. Following 10 weeks of daily 1-hr sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0 mg/kg) was injected s.c. immediately or 4-hr prior to PSR or relapse testing. Results Injections of nicotine immediately prior to testing reduced (5–10 responses PSR; 50–60 responses relapse), whereas injections of nicotine 4-hr prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0 mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Discussion The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time-dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH whereas, with a delay of 4-hr, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine’s metabolites (i.e., cotinine, nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors. PMID:21689122

  9. A prospective study of off-label use of, abuse of, and dependence on nicotine inhaler

    PubMed Central

    Hughes, J; Adams, E; Franzon, M; Maguire, M; Guary, J

    2005-01-01

    Objective: To determine the incidence of off-label use of, abuse of, and dependence on prescription nicotine inhaler. Design: Prospective telephone and internet interviews for six months. Participants: 535 new inhaler users. Main outcome: Structured interview about off-label use (that is, use of inhaler for non-cessation reasons or concurrent use of inhaler and cigarettes) and Diagnostic and statistical manual, fourth edition (DSM-IV) and International classification of diseases, 10th edition (ICD-10) criteria for abuse and dependence Results: Although many used inhaler and cigarettes concurrently at some time (43–55%), few used inhaler for non-cessation reasons (4–9%) and few persisted in off label use (8–16%; 95% confidence interval (CI) 5% to 19%). No participant met ICD-10 criteria for harmful use/abuse (95% CI 0% to 3.3%). Eight subjects (1.4%) appeared to meet DSM-IV or ICD-10 criteria for dependence on inhaler, but none were found dependent in a clinical expert interview (95% CI 0% to 3.3%). Conclusions: Although transient concurrent use of inhaler and cigarettes often occurs, use for non-cessation reasons, abuse and dependence are rare. PMID:15735300

  10. A multiancestry study identifies novel genetic associations with CHRNA5 methylation in human brain and risk of nicotine dependence

    PubMed Central

    Hancock, Dana B.; Wang, Jen-Chyong; Gaddis, Nathan C.; Levy, Joshua L.; Saccone, Nancy L.; Stitzel, Jerry A.; Goate, Alison; Bierut, Laura J.; Johnson, Eric O.

    2015-01-01

    Nicotine dependence is influenced by chromosome 15q25.1 single nucleotide polymorphisms (SNPs), including the missense SNP rs16969968 that alters function of the α5 nicotinic acetylcholine receptor (CHRNA5) and noncoding SNPs that regulate CHRNA5 mRNA expression. We tested for cis-methylation quantitative trait loci (cis-meQTLs) using SNP genotypes and DNA methylation levels measured across the IREB2-HYKK-PSMA4-CHRNA5-CHRNA3-CHRNB4 genes on chromosome 15q25.1 in the BrainCloud and Brain QTL cohorts [total N = 175 European-Americans and 65 African-Americans (AAs)]. We identified eight SNPs that were significantly associated with CHRNA5 methylation in prefrontal cortex: P ranging from 6.0 × 10−10 to 5.6 × 10−5. These SNP–methylation associations were also significant in frontal cortex, temporal cortex and pons: P ranging from 4.8 × 10−12 to 3.4 × 10−3. Of the eight cis-meQTL SNPs, only the intronic CHRNB4 SNP rs11636753 was associated with CHRNA5 methylation independently of the known SNP effects in prefrontal cortex, and it was the most significantly associated SNP with nicotine dependence across five independent cohorts (total N = 7858 European ancestry and 3238 AA participants): P = 6.7 × 10−4, odds ratio (OR) [95% confidence interval (CI)] = 1.11 (1.05–1.18). The rs11636753 major allele (G) was associated with lower CHRNA5 DNA methylation, lower CHRNA5 mRNA expression and increased nicotine dependence risk. Haplotype analyses showed that rs11636753-G and the functional rs16969968-A alleles together increased risk of nicotine dependence more than each variant alone: P = 3.1 × 10−12, OR (95% CI) = 1.32 (1.22–1.43). Our findings identify a novel regulatory SNP association with nicotine dependence and connect, for the first time, previously observed differences in CHRNA5 mRNA expression and nicotine dependence risk to underlying DNA methylation differences. PMID:26220977

  11. Prevalence and correlates of nicotine dependence among construction site workers: A cross-sectional study in Delhi

    PubMed Central

    Parashar, Mamta; Agarwalla, Rashmi; Mallik, Praveen; Dwivedi, Shridhar; Patvagekar, Bilkish; Pathak, Rambha

    2016-01-01

    Introduction: Workers represent half the world's population and are major contributors to economic and social development. Tobacco consumption in construction site workers has been considered a big challenge. Objectives: (1) To assess the prevalence of nicotine dependence among tobacco users. (2) To study the correlates of nicotine dependence among the construction site workers. Methodology: A cross sectional study was conducted using a predesigned and pretested structured proforma. The study was conducted among all construction site workers aged 18yrs and above in campus of Hamdard Institute of Medical Sciences and Research and associated HAH centenary hospital, New Delhi. Karl Fagerstrom Nicotine Dependence Questionnaire was used to assess dependence on nicotine. Results: The mean age of construction site workers was 32.04±11.6 years. Among the workers, majority (91%) were tobacco user. Among the users, 60% found it difficult to refrain from smoking/chewing in places where use of tobacco is not allowed (e.g. hospitals, government offices, cinemas, Libraries etc). 55% of the users smoked or chewed tobacco during the first hours after waking than during the rest of the day. On multivariate analysis, the factors which were found to be significantly associated with nicotine dependence were lower income group (OR 2.57, CI:1.66-3.99), smokeless tobacco use (OR 2.36, CI:1.30-4.27) and lower education (OR = 2.86 (95% CI 1.97-4.16) for illiterate). Discussion: The prevalence of tobacco use (91%) among construction workers is very high compared to that in the general population. Recognition of construction sites as work places and proper implementation of law is needed.

  12. Prevalence and correlates of nicotine dependence among construction site workers: A cross-sectional study in Delhi

    PubMed Central

    Parashar, Mamta; Agarwalla, Rashmi; Mallik, Praveen; Dwivedi, Shridhar; Patvagekar, Bilkish; Pathak, Rambha

    2016-01-01

    Introduction: Workers represent half the world's population and are major contributors to economic and social development. Tobacco consumption in construction site workers has been considered a big challenge. Objectives: (1) To assess the prevalence of nicotine dependence among tobacco users. (2) To study the correlates of nicotine dependence among the construction site workers. Methodology: A cross sectional study was conducted using a predesigned and pretested structured proforma. The study was conducted among all construction site workers aged 18yrs and above in campus of Hamdard Institute of Medical Sciences and Research and associated HAH centenary hospital, New Delhi. Karl Fagerstrom Nicotine Dependence Questionnaire was used to assess dependence on nicotine. Results: The mean age of construction site workers was 32.04±11.6 years. Among the workers, majority (91%) were tobacco user. Among the users, 60% found it difficult to refrain from smoking/chewing in places where use of tobacco is not allowed (e.g. hospitals, government offices, cinemas, Libraries etc). 55% of the users smoked or chewed tobacco during the first hours after waking than during the rest of the day. On multivariate analysis, the factors which were found to be significantly associated with nicotine dependence were lower income group (OR 2.57, CI:1.66-3.99), smokeless tobacco use (OR 2.36, CI:1.30-4.27) and lower education (OR = 2.86 (95% CI 1.97-4.16) for illiterate). Discussion: The prevalence of tobacco use (91%) among construction workers is very high compared to that in the general population. Recognition of construction sites as work places and proper implementation of law is needed. PMID:27625442

  13. The contribution of rare and common variants in 30 genes to risk nicotine dependence.

    PubMed

    Yang, J; Wang, S; Yang, Z; Hodgkinson, C A; Iarikova, P; Ma, J Z; Payne, T J; Goldman, D; Li, M D

    2015-11-01

    Genetic and functional studies have revealed that both common and rare variants of several nicotinic acetylcholine receptor subunits are associated with nicotine dependence (ND). In this study, we identified variants in 30 candidate genes including nicotinic receptors in 200 sib pairs selected from the Mid-South Tobacco Family population with equal numbers of African Americans (AAs) and European Americans (EAs). We selected 135 of the rare and common variants and genotyped them in the Mid-South Tobacco Case-Control (MSTCC) population, which consists of 3088 AAs and 1430 EAs. None of the genotyped common variants showed significant association with smoking status (smokers vs non-smokers), Fagerström Test for ND scores or indexed cigarettes per day after Bonferroni correction. Rare variants in NRXN1, CHRNA9, CHRNA2, NTRK2, GABBR2, GRIN3A, DNM1, NRXN2, NRXN3 and ARRB2 were significantly associated with smoking status in the MSTCC AA sample, with weighted sum statistic (WSS) P-values ranging from 2.42 × 10(-3) to 1.31 × 10(-4) after 10(6) phenotype rearrangements. We also observed a significant excess of rare nonsynonymous variants exclusive to EA smokers in NRXN1, CHRNA9, TAS2R38, GRIN3A, DBH, ANKK1/DRD2, NRXN3 and CDH13 with WSS P-values between 3.5 × 10(-5) and 1 × 10(-6). Variants rs142807401 (A432T) and rs139982841 (A452V) in CHRNA9 and variants V132L, V389L, rs34755188 (R480H) and rs75981117 (N549S) in GRIN3A are of particular interest because they are found in both the AA and EA samples. A significant aggregate contribution of rare and common coding variants in CHRNA9 to the risk for ND (SKAT-C: P=0.0012) was detected by applying the combined sum test in MSTCC EAs. Together, our results indicate that rare variants alone or combined with common variants in a subset of 30 biological candidate genes contribute substantially to the risk of ND. PMID:25450229

  14. Effects of Menthol on Nicotine Pharmacokinetic, Pharmacology and Dependence in Mice

    PubMed Central

    Alsharari, Shakir D.; King, Justin R.; Nordman, Jacob C.; Muldoon, Pretal P.; Jackson, Asti; Zhu, Andy Z. X.; Tyndale, Rachel F.; Kabbani, Nadine; Damaj, M. Imad.

    2015-01-01

    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. PMID:26355604

  15. Protein dependent fate of hepatic cells under nicotine induced stress and curcumin ameliorated condition.

    PubMed

    Banerjee, Satyam; Chattopadhyay, Krishna; Chhabra, Jasmeet Kaur; Chattopadhyay, Brajadulal

    2012-06-01

    Nicotine is mainly metabolized in liver. Its abuse elicits acute phase response by activating macrophages to produce pro-inflammatory cytokines, which play critical role in apoptosis or cell proliferation. The protective pharmacological mechanism of curcumin against nicotine-induced toxicity on protein malnourished liver is still remaining unclear. This study investigated the ameliorative mechanism of curcumin against nicotine-induced toxicity and also fate of liver particularly under protein restricted condition. Female Albino-rats maintained under normal/protein-restricted diets, were subcutaneously injected with nicotine tartrate (2.5 mg/kg body weight/day) and orally supplemented with curcumin (80 mg/kg body weight/day) for 21 days. The animals were then sacrificed to dissect out liver and proceed with further experiments. Interactions of nicotine with DNA both in vivo and in vitro were observed by thermal denaturation and DNA laddering assays. Effects of nicotine on hepatic cells were monitored by differential staining, comet assay, cytokine profiling, mRNA and protein expression. Nicotine caused more intense DNA damage, promoted hepatic cell death through up-regulating pro-apoptotic proteins and signaling molecules in protein malnourished individuals. Through up-regulation of anti-apoptotic proteins and proliferation promoting molecules, nicotine dysregulated homeostasis in normal protein condition. Curcumin significantly ameliorated the nicotine-induced toxicity in both conditions and regulated the imbalance between cell survival and death induced by nicotine. The protein content present in the nicotine induced hepatic cell decides either cell-survival pathway or cytotoxic pathway. PMID:22381069

  16. A Self-Efficacy Scale for Chemical Dependency in Adolescence.

    ERIC Educational Resources Information Center

    St. Mary, Sharon; Russo, Thomas J.

    This study was conducted to develop a scale that assesses perceptions of self-efficacy in potentially stressful situations for chemically dependent adolescents. Adolescent subjects (N=100) currently receiving treatment for chemical dependency were given a 20-situation questionnaire, the Adolescent Self-Efficacy Scale (ASES). Students were…

  17. The Role of Constraint in the Development of Nicotine, Marijuana, and Alcohol Dependence in Young Adulthood

    PubMed Central

    Vrieze, Scott I.; Vaidyanathan, Uma; Hicks, Brian M.; Iacono, William G.; McGue, Matt

    2014-01-01

    The personality-related construct of behavioral disinhibition is hypothesized to confer a generalized risk for alcohol and drug dependence. On average, rates of substance use and scores on measures of disinhibition peak in adolescence and decline as people mature into adulthood. The present study investigated this developmental change by evaluating the relationship between disinhibition and substance use disorders using a longitudinal study of 2,608 twins assessed at ages 17, 24, and 29. These ages include the period of highest risk for substance use disorders (ages 17-24) as well as when substance dependence symptoms typically decline (ages 24-29). Disinhibition was measured with the Multidimensional Personality Questionnaire higher-order scale of Constraint, as well as its constituent facet scales of Harm Avoidance, Control, and Traditionalism. Constraint’s relationship with substance dependence was statistically significant but small and largely genetic, with the genetic relationship declining from adolescence into adulthood. However, this result appeared to be almost entirely driven by Traditionalism, a propensity to hold traditional moral and social values, and not an obvious component of behavioral disinhibition. The results suggest that personality measures of Control and Harm Avoidance play only a small role in the development of substance dependence during late adolescence, and previous findings linking personality measures of disinhibition and substance use may be driven significantly by social and moral values than deficits in impulse control. PMID:24343204

  18. Nicotine induced pro-oxidant and antioxidant imbalance in rat lymphocytes: in vivo dose and time dependent approaches.

    PubMed

    Das, Subhasis; Chakraborty, Subhankari Prasad; Roy, Soumyabrata; Roy, Somenath

    2012-11-01

    The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was undertaken to determine the dose as well as time dependent effects of nicotine administration on the superoxide anion generation, lipid peroxidation and antioxidant defense systems in lymphocytes. Male Wistar rats were treated with vehicle (normal saline) and nicotine [3-(1-methyl-2-pyrrolidinyl) pyridine, C(10)H(14)N(2)] (in physiological saline, pH was adjusted at 7.4 prior to injection) as indicated in a dose and duration fashion and the superoxide anion generation, lipid peroxidation, and antioxidant enzymes status were monitored. Superoxide anion generation, lipid peroxidation and oxidized glutathione levels were increased significantly (P < 0.05), and reduced glutathione level, activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-s-transferase were decreased significantly (P < 0.05) with the increasing dose and duration of nicotine treatment. The highest changes in lymphocytes were observed at the dose of 1.0 mg/kg/day for 7 days. It may be concluded that nicotine is able to enhance the production of ROS that produced oxidative stress in lymphocytes in a dose and time dependent manner. PMID:22894698

  19. Nicotine poisoning

    MedlinePlus

    Nicotine is found in: Chewing tobacco Cigarettes E-cigarettes Liquid nicotine Nicotine gum (Nicorette) Nicotine patches (Habitrol, Nicoderm) Pipe tobacco Some insecticides Tobacco leaves Note: This list may not be all-inclusive.

  20. Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine.

    PubMed

    Poorthuis, Rogier B; Bloem, Bernard; Verhoog, Matthijs B; Mansvelder, Huibert D

    2013-03-13

    Adolescence is a period in which the developing prefrontal cortex (PFC) is sensitive to maladaptive changes when exposed to nicotine. Nicotine affects PFC function and repeated exposure to nicotine during adolescence impairs attention performance and impulse control during adulthood. Nicotine concentrations experienced by smokers are known to desensitize nicotinic acetylcholine receptors (nAChRs), but the impact thereof on PFC circuits is poorly understood. Here, we investigated how smoking concentrations of nicotine (100-300 nm) interfere with cholinergic signaling in the mouse PFC. nAChR desensitization depends on subunit composition. Since nAChR subunits are differentially expressed across layers of the PFC neuronal network, we hypothesized that cholinergic signaling through nAChRs across layers would suffer differentially from exposure to nicotine. Throughout the PFC, nicotine strongly desensitized responses to ACh in neurons expressing β2* nAChRs, whereas ACh responses mediated by α7 nAChRs were not hampered. The amount of desensitization of β2* nAChR currents depended on neuron type and cortical layer. β2*-mediated responses of interneurons in LII-III and LVI completely desensitized, while cholinergic responses in LV interneurons and LVI pyramidal cells showed less desensitization. This discrepancy depended on α5 subunit expression. Two-photon imaging of neuronal population activity showed that prolonged exposure to nicotine limited cholinergic signaling through β2* nAChRs to deep PFC layers where α5 subunits were expressed. Together, our results demonstrate a layer-dependent decrease in cholinergic activation of the PFC through nAChRs by nicotine. These mechanisms may be one of the first steps leading up to the pathophysiological changes associated with nicotine exposure during adolescence.

  1. Effects of cigarette smoking and nicotine dependence on adherence to antiretroviral therapy among HIV-positive patients in Vietnam.

    PubMed

    Nguyen, Nhung T P; Tran, Bach X; Hwang, Lu Y; Markham, Christine M; Swartz, Michael D; Vidrine, Jennifer I; Phan, Huong T T; Latkin, Carl A; Vidrine, Damon J

    2016-01-01

    Cigarette smoking is increasingly recognized as an indicator for inferior adherence to antiretroviral therapy (ART) among HIV-positive patients. Given the limited body of work on this issue, we aimed to explore the relations between cigarette smoking, nicotine dependence, and ART adherence in Vietnam. A cross-sectional study of 1050 HIV-positive people was conducted from January to September 2013 in Hanoi (the capital) and Nam Dinh (a rural city). Adherence to ART during the last 30 days was measured by the 100-point visual analog scale (VAS). Smoking history and nicotine dependence (Fagerstrom Test of Nicotine Dependence) were self-reported by participants. Multiple logistic regression was performed to examine the association of current smoking and nicotine dependence with ART nonadherence. Using the established VAS cut point of 95 to indicate adequate adherence, the prevalence of ART nonadherence was 30.9%. Approximately 35.5% of the sample reported current smoking. No association between smoking status and ART nonadherence was found. However, participants with greater nicotine dependence (OR = 1.1, 95%CI = 1.0-1.2 per unit increase) were more likely to be nonadherent. Also, individuals who were female (OR = 1.70, 95%CI = 1.19-2.42), receiving ART in Nam Dinh (OR = 1.6, 95%CI = 1.1-2.4), and currently feeling anxiety (OR = 1.6, 95% CI = 1.2-2.1) had a higher likelihood of ART nonadherence. Additionally, current smokers reporting current pain (OR = 1.9, 95%CI = 1.2-3.1) were more likely to be nonadherent. Conversely, protective factors included living with a spouse/partner (OR = 0.5, 95%CI = 0.3-0.7) and having more than a high school education (OR = 0.4, 95%CI = 0.1-1.0). Given the high prevalence of suboptimal adherence and current smoking among HIV-positive patients, screening for smoking status and nicotine dependence during ART treatment may help to improve patients' adherence to medication. More efforts

  2. In vitro nicotine-induced oxidative stress in mice peritoneal macrophages: a dose-dependent approach.

    PubMed

    Mahapatra, Santanu Kar; Das, Subhasis; Bhattacharjee, Surajit; Gautam, N; Majumdar, Subrata; Roy, Somenath

    2009-02-01

    The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. In the present study, peritoneal macrophages (6 x 10(6) cells, >95% viable) isolated from male Swiss mice were treated with nicotine (1 mM, 5 mM, 10 mM, 25 mM, and 50 mM) in vitro for 12 h and the superoxide anion generation, lipid peroxidation, protein oxidation and antioxidant enzymes status were monitored. Maximum superoxide radical generation was found at the dose of 10 mM nicotine. The lipid peroxidation and protein oxidation were increased significantly (p < 0.05) along with the increasing dose of nicotine. The reduced glutathione level, catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities were decreased significantly (p < 0.05), and oxidized glutathione level was increased significantly (p < 0.05) with the increasing dose of the nicotine. From these experiments, it was also observed that all the changes in peritoneal macrophages with 10 mM, 25 mM, and 50 mM nicotine had no significant difference. To observe the effect of nicotine in vivo, this study examined the liver and spleen antioxidant status after nicotine administration (1 mg/kg BW) intraperitoneally in mice and found the diminished SOD activity and GSH level. It may be concluded that nicotine is able to enhance the production of ROS that produced oxidative stress in murine peritoneal macrophages. It also suggested that, 10 mM in vitro nicotine treatment for 12 h is the effective dose. PMID:19778253

  3. The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

    PubMed Central

    Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

    2015-01-01

    Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

  4. Smoking initiation and nicotine dependence symptoms in Ukraine: Findings from the Ukraine World Mental Health survey

    PubMed Central

    Webb, Charles P.M.; Bromet, Evelyn J.; Tintle, Nathan L.; Schwartz, Joseph E.; Gluzman, Semyon F.; Kostyuchenko, Stanislav; Havenaar, Johan M.

    2007-01-01

    Summary Objectives Cigarette smoking is a major cause of morbidity and mortality in former Soviet countries. This study examined the personal, familial and psychiatric risk factors for smoking initiation and development of nicotine dependence symptoms in Ukraine. Study Design Cross-sectional survey. Methods Smoking history and dependence symptoms were ascertained from N=1,711 adults in Ukraine as part of a national mental health survey conducted in 2002. Separate analyses were conducted for men and women. Results The prevalence of lifetime regular smoking was 80.5% in men and 18.7% in women, with median ages at initiation among smokers of 17 and 18, respectively. Furthermore, 61.2% of men and 11.9% of women were current smokers; among the subgroup of lifetime smokers, 75.9% of men and 63.1% of women currently smoked. The youngest female cohort (born 1965–1984) was 26 times more likely to start smoking than the oldest. Smoking initiation was also linked to childhood externalizing behaviors and antecedent use of alcohol in both genders, as well as marital status and personal alcohol abuse in men, and childhood urbanicity and birth cohort in women. Dependence symptoms developed in 61.7% of male and 47.1% of female smokers. The rate increased sharply in the first four years after smoking initiation. Dependence symptoms were related to birth cohort and alcohol abuse in both genders, as well as growing up in a suburb or town and childhood externalizing behaviors in men, and parental antisocial behavior in women. Conclusions Increased smoking in young women heralds a rising epidemic in Ukraine and underscores the need for primary prevention programs, especially in urban areas. Our findings support the importance of childhood and alcohol-related risk factors, especially in women, while pre-existing depression and anxiety disorders were only weakly associated with starting to smoke or developing dependence symptoms. PMID:17544466

  5. Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence

    PubMed Central

    Hancock, D B; Reginsson, G W; Gaddis, N C; Chen, X; Saccone, N L; Lutz, S M; Qaiser, B; Sherva, R; Steinberg, S; Zink, F; Stacey, S N; Glasheen, C; Chen, J; Gu, F; Frederiksen, B N; Loukola, A; Gudbjartsson, D F; Brüske, I; Landi, M T; Bickeböller, H; Madden, P; Farrer, L; Kaprio, J; Kranzler, H R; Gelernter, J; Baker, T B; Kraft, P; Amos, C I; Caporaso, N E; Hokanson, J E; Bierut, L J; Thorgeirsson, T E; Johnson, E O; Stefansson, K

    2015-01-01

    We conducted a 1000 Genomes–imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerström Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 × 10−9 across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08–1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 × 10−4). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00–1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single ‘cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences. PMID:26440539

  6. An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence

    PubMed Central

    Frahm, Silke; Antolin-Fontes, Beatriz; Görlich, Andreas; Zander, Johannes-Friedrich; Ahnert-Hilger, Gudrun; Ibañez-Tallon, Ines

    2015-01-01

    A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior. DOI: http://dx.doi.org/10.7554/eLife.11396.001 PMID:26623516

  7. Comparison of nicotine dependence indicators in predicting quitting among pregnant smokers.

    PubMed

    Kurti, Allison N; Davis, Danielle R; Skelly, Joan M; Redner, Ryan; Higgins, Stephen T

    2016-02-01

    Research in the general population of smokers indicates that across various measures of nicotine dependence, time to first cigarette (TTFC) is the strongest single-item predictor of quitting success. Whether those findings generalize to pregnant smokers is unclear. To investigate this matter, we compared TTFC with cigarettes per day (CPD) and the Heaviness of Smoking Index (HSI; Kozlowski, Porter, Orleans, Pope, & Heatherton, 1994) in predicting late-pregnancy abstinence among 289 pregnant women enrolled in 4 smoking-cessation trials assessing the efficacy of financial incentives. Logistic regression was used to compare predictors, with model fit measured using the c statistic (range = 0.5, poor prediction to 1.0, perfect prediction). In simple regressions, model fit was comparable across the 3 measures although strongest for CPD alone (c = 0.70, 0.68, 0.66 for CPD, HSI, and TTFC, respectively). In a stepwise multiple regression, treatment was entered first (c = 0.67), then CPD (c = 0.77), quit attempts prepregnancy (c = .81), TTFC (c = .82), and quit attempts during pregnancy (c = .83). We saw no evidence supporting TTFC as the optimal predictor of quitting among pregnant smokers. Instead, the evidence supported using CPD and TTFC together or CPD alone if using only a single predictor. PMID:27046504

  8. Withdrawal From Chronic Nicotine Reduces Thyroid Hormone Levels and Levothyroxine Treatment Ameliorates Nicotine Withdrawal-Induced Deficits in Hippocampus-Dependent Learning in C57BL/6J Mice

    PubMed Central

    Leach, Prescott T.; Holliday, Erica; Kutlu, Munir G.

    2015-01-01

    Introduction: Cigarette smoking alters a variety of endocrine systems including thyroid hormones. Altered thyroid hormone signaling may lead to a subclinical or overt hypothyroid condition that could contribute to nicotine withdrawal-related symptoms, such as cognitive deficits. Thus, normalizing thyroid hormone levels may represent a novel therapeutic target for ameliorating nicotine withdrawal-associated cognitive deficits. Methods: The current studies conducted an analysis of serum thyroid hormone levels after chronic and withdrawal from chronic nicotine treatment in C57BL/6J mice using an enzyme-linked immunosorbent assay. The present studies also evaluated the effect of synthetic thyroid hormone (levothyroxine) on contextual and cued memory. Results: The current studies found that nicotine withdrawal reduces secreted thyroid hormone levels by 9% in C57BL/6J mice. Further, supplemental thyroid hormone not only enhanced memory in naïve animals, but also ameliorated deficits in hippocampus-dependent learning associated with nicotine withdrawal. Conclusions: These results suggest that smokers attempting to quit should be monitored closely for changes in thyroid function. If successfully treated, normalization of thyroid hormone levels may ameliorate some deficits associated with nicotine withdrawal and this may lead to higher rates of successful abstinence. PMID:25358661

  9. Nicotine and cannabinoids: parallels, contrasts and interactions.

    PubMed

    Viveros, Maria-Paz; Marco, Eva M; File, Sandra E

    2006-01-01

    After a brief outline of the nicotinic and cannabinoid systems, we review the interactions between the pharmacological effects of nicotine and cannabis, two of the most widely used drugs of dependence. These drugs are increasingly taken in combination, particularly among the adolescents and young adults. The review focuses on addiction-related processes, gateway and reverse gateway theories of addiction and therapeutic implications. It then reviews studies on the important period of adolescence, an area that is in urgent need of further investigation and in which the importance of sex differences is emerging. Three other areas of research, which might be particularly relevant to the onset and/or maintenance of dependence, are then reviewed. Firstly, the effects of the two drugs on anxiety-related behaviours are discussed and then their effects on food intake and cognition, two areas in which they have contrasting effects. Certain animal studies suggest that reinforcing effects are likely to be enhanced by joint consumption of nicotine and cannabis, as also may be anxiolytic effects. If this was the case in humans, the latter might be viewed as an advantage particularly by adolescent girls, although the increased weight gain associated with cannabis would be a disadvantage. The two drugs also have opposite effects on cognition and the possibility of long-lasting cognitive impairments resulting from adolescent consumption of cannabis is of particular concern.

  10. Cue reactivity in cannabis-dependent adolescents.

    PubMed

    Nickerson, Lisa D; Ravichandran, Caitlin; Lundahl, Leslie H; Rodolico, John; Dunlap, Steven; Trksak, George H; Lukas, Scott E

    2011-03-01

    The authors measured event-related potentials with a craving manipulation to investigate the neural correlates of drug cue reactivity in 13 adolescents who are cannabis dependent (CD; ages 14-17). The P300 responses to marijuana (MJ) pictures (MJ-P300) and control pictures (C-P300) were assessed after handling neutral objects and again after handling MJ paraphernalia (MJP). Self-reported drug craving and heart rates also were measured. MJ-P300 were larger than C-P300 (p < .001), and both the MJ-P300 and craving increased significantly after handling MJP (p = .002 and p = .003, respectively), with no association between the magnitude of craving and MJ-P300. Heart rates were not affected by handling MJP. The results showed that adolescents who are CD have an attentional bias to MJ stimuli that increases after handling marijuana paraphernalia. Generally, the results are consistent with what has been reported for adult heavy chronic cannabis smokers, although there were some differences that require further investigation. PMID:21142334

  11. Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio.

    PubMed

    Allenby, Cheyenne E; Boylan, Kelly A; Lerman, Caryn; Falcone, Mary

    2016-09-01

    Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation. PMID:26872457

  12. Strain-Dependent Performance in Nicotine-Induced Conditioned Place Preference

    PubMed Central

    Kutlu, Munir G.; Ortega, Leonardo A.; Gould, Thomas J.

    2015-01-01

    Nicotine addiction is most likely a result of a combination of factors including the rewarding effects of the drug; these effects, however, might be influenced by genetic background. Using a conditioned place preference (CPP) paradigm and 8 inbred mouse strains, we conducted an initial examination of the role of genetic background in the rewarding effects of nicotine. Following habituation and initial place preference test, inbred strains (A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, CBA/J, DBA/1J, DBA/2J, and 129/SvEv) were trained and tested in CPP for nicotine (0.35 mg/kg). Although several strains (C57BL/6J, CBA/J, and 129/SvEv) showed nicotine-induced CPP, 1 strain (DBA/1J) showed conditioned place aversion (CPA), and other strains (A/J, BALB/cByJ, C3H/HeJ, and DBA/2J) did not show CPP. Overall, these results indicate that nicotine’s rewarding effects tested in CPP are differentially affected by the genetic background, and this trait has a relatively high heritability (42%–57%). This initial investigation lays the foundation for future studies examining the genetic substrates of nicotine reward. PMID:25546366

  13. Nicotine Lozenges

    MedlinePlus

    Nicotine lozenges are used to help people stop smoking. Nicotine lozenges are in a class of medications called smoking cessation aids. They work by providing nicotine to your body to decrease the withdrawal symptoms ...

  14. Chronic administration of nicotine-free cigarette smoke extract impaired endothelium-dependent vascular relaxation in rats via increased vascular oxidative stress.

    PubMed

    Shimosato, Takashi; Geddawy, Ayman; Tawa, Masashi; Imamura, Takeshi; Okamura, Tomio

    2012-01-01

    Cigarette smoking has been implicated in the initiation and progression of cardiovascular disorders and atherosclerosis. Here, we examined the effects of nicotine-free cigarette smoke extract (CSE) on the regulation of cardiovascular function. Rats were subcutaneously administered PBS or nicotine-free CSE at 0.05 to 1.5 mL/day per rat for 4 weeks. Blood pressure, cardiac function, and vascular responsiveness were measured at 4 weeks after administration. Furthermore, acute effects of nicotine-free CSE were also studied in the aorta isolated from normal rats. Blood pressure and left ventricular systolic pressure (LVSP) were significantly increased in the nicotine-free CSE-administered rats, but heart rate, dP/dt(max), and dP/dt(min) were not affected. Endothelium-dependent relaxation by acetylcholine (ACh) in the nicotine-free CSE-treated rats was significantly attenuated compared to PBS-treated rats, but endothelium-independent relaxation by sodium nitroprusside (SNP) did not differ. Pretreatment with superoxide dismutase restored the attenuated ACh-induced relaxation. Contractions by phenylephrine, angiotensin II, and KCl did not differ between two groups. In vitro acute nicotine-free CSE treatment did not alter the response to ACh or SNP. These results suggest that chronic nicotine-free CSE administration impairs endothelial function by increased production of superoxide derived from the vascular wall components other than smooth muscles and induces slight hypertension accompanied with LVSP elevation.

  15. Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: A 40-year prospective study

    PubMed Central

    Stroud, Laura R.; Papandonatos, George; Shenassa, Edmond; Rodriguez, Daniel; Niaura, Raymond; LeWinn, Kaja; Lipsitt, Lewis P.; Buka, Stephen L.

    2013-01-01

    Background Maternal smoking during pregnancy (MSDP) is an independent risk factor for offspring nicotine dependence (ND), but mechanisms remain unknown. We investigated prenatal glucocorticoid (cortisol) and androgen (testosterone) associations with offspring ND over 40 years, and the possibility that prenatal glucocorticoids and androgens would mediate links between MSDP and offspring ND. Methods Participants were 1,086 mother-adult offspring pairs (59% female) from the New England Family Study, a 40-year longitudinal follow up of the Collaborative Perinatal Project. MSDP was assessed prospectively at each prenatal visit. Maternal cortisol, testosterone, and cotinine (nicotine metabolite), were assayed from third trimester maternal sera. Offspring lifetime ND was assessed via structured interview. Results Significant bivariate associations emerged for: a) MSDP/cotinine and lifetime ND, and b) maternal cortisol and lifetime ND, for daughters only. In multivariate models, maternal cortisol and MSDP/cotinine remained significantly and independently associated with increased odds of daughters’ lifetime ND. However, cortisol did not mediate the MSDP-lifetime ND relation. No associations emerged between maternal testosterone and offspring ND. Conclusions Results provide the first evidence in support of prenatal glucocorticoid programming of adult ND over 40 years in daughters only. Our study highlights two independent prenatal pathways leading to increased risk for ND in daughters: elevated prenatal glucocorticoids and MSDP/nicotine exposure. Daughter-specific effects of glucocorticoid and MSDP programming over 40 years highlight the breadth and persistence of sexually dimorphic programming effects in humans. Results do not support androgen programming of offspring ND. PMID:24034414

  16. The Association between Cue-Reactivity in the Precuneus and Level of Dependence on Nicotine and Alcohol*

    PubMed Central

    Courtney, Kelly E.; Ghahremani, Dara G.; London, Edythe D.; Ray, Lara A.

    2014-01-01

    Background Given numerous reports implicating involvement of the precuneus in cue-reactivity paradigms, the goal of this investigation was to examine the relationship between activation of the precuneus in response to drug cues and measures of subjective craving and severity of dependence in volunteers who were comorbid for alcohol and nicotine abuse. Methods Forty research participants, who all reported heavy drinking and daily smoking, were recruited (15 women; 70% Caucasian; mean age = 31.2 years) for a functional magnetic resonance imaging (fMRI) session involving a cigarette video-cues task and an alcohol taste-cues task. Mean precuneus activation from both tasks during cue presentation was subjected to bivariate correlation analyses with indices of dependence severity and subjective craving. Results Precuneus activation in the contrast of Cigarette Cues vs. Control Cues was positively correlated with scores on the Fagerström Test of Nicotine Dependence (r=0.389, p=0.016), and activation in the Alcohol Cues vs. Control Cues contrast was positively correlated with Alcohol Dependence Scale scores (r=0.338, p=0.038). No correlations with subjective craving were observed (ps>0.05). Conclusions These findings indicate that the precuneus is involved in cue reactivity for both cigarettes and alcohol, and that this involvement is moderated by severity of drug dependence. The precuneus may be a cortical locus for neuroplastic changes related to drug dependence. PMID:24880692

  17. Study finds stronger nicotine dependency associated with higher risk of lung cancer

    Cancer.gov

    NCI headed study finds people who are highly addicted to nicotine -- those who smoke their first cigarette within five minutes after awakening -- are at higher risk of developing lung cancer than those who wait for an hour or more to smoke.

  18. Nicotine dependence in the mental disorders, relationship with clinical indicators, and the meaning for the user1

    PubMed Central

    de Oliveira, Renata Marques; Carlos Siqueira, Antônio; Santos, Jair Lício Ferreira; Furegato, Antonia Regina Ferreira

    2014-01-01

    OBJECTIVE: to identify the degree of nicotine dependence among patients with schizophrenia and other mental disorders hospitalized in a general hospital, correlating these indices with clinical indicators and the meaning for the user. METHOD: the study was performed in the psychiatric unit of a general hospital, interviewing 270 patients with mental disorders using a questionnaire and the application of the Fagerstrom test. A descriptive statistical analysis of the data and thematic analysis of the content were performed. RESULTS: among the 270 patients with mental disorders, 35.6% were smokers; of whom, 53.2% presented high or very high nicotine dependence. Of the 96 smokers, 32 (33.3%) were schizophrenic, among whom, 59.4% presented high or very high dependence. Higher levels of dependence were also found among the 59 elderly people (61.5%) and 60 subjects with somatic comorbidities (62.5%). Meanings of smoking for the subjects: helps to forget problems and face daily conflicts; alleviates side effects of the medications; self-control; distraction; part of life. CONCLUSION: more intense tobacco dependence among schizophrenic patients is justified due to it helping them to cope with the difficulties of the disease. Nurses occupy a strategic position in the care. PMID:25296154

  19. Correlation between nicotine dependence and barriers to cessation between exclusive cigarette smokers and dual (water pipe) smokers among Arab Americans

    PubMed Central

    El-Shahawy, Omar; Haddad, Linda

    2015-01-01

    Background Evidence suggests that dual cigarette and water pipe use is growing among minority groups, particularly among Arab Americans. Differences in nicotine dependence and barriers to smoking cessation among such dual smokers have not been previously examined in this population. We examined potential differences that might exist between exclusive cigarette smokers and dual smokers (cigarette and water pipe) pertaining to nicotine dependence and barriers to cessation among Arab Americans. Methods We conducted a cross-sectional study using a convenience sample of self-identified Arab immigrant smokers (n=131) living in the Richmond, VA metropolitan area. Data were collected using four questionnaires: Demographic and Cultural Information questionnaire, Tobacco Use questionnaire, Fagerström Test for Nicotine Dependence (FTND) questionnaire, and Barriers to Cessation questionnaire. We examined differences in nicotine dependence and barriers to cessation between exclusive cigarette smokers and dual smokers of cigarettes and water pipe. Furthermore, we explored the correlations of these measures with select variables. Results There was a significant difference in the FTND scores between the exclusive cigarette smokers (mean M=2.55, standard deviation [SD] =2.10) and dual smokers (M=3.71, SD =2.42); t(129) = (2.51), P=0.0066. There was also a significant difference in the Barriers to Cessation scores between exclusive cigarette smokers (M=38.47, SD =13.07) and dual smokers (M=45.21, SD =9.27); t(129) = (2.56), P=0.0058. Furthermore, there was a highly significant correlation among FTND scores, Barriers to Cessation scores, and past quit attempts among dual smokers. Conclusion Water pipe tobacco smoking seems to be both adding to the dependence potential of cigarette smoking and enhancing barriers to cessation in our study sample. However, the high correlation between quit attempts, FTND, and barriers to cessation needs further investigation to ascertain the possible

  20. A mechanistic hypothesis of the factors that enhance vulnerability to nicotine use in females

    PubMed Central

    O'Dell, Laura E.; Torres, Oscar V.

    2013-01-01

    Women are particularly more vulnerable to tobacco use than men. This review proposes a unifying hypothesis that females experience greater rewarding effects of nicotine and more intense stress produced by withdrawal than males. We also provide a neural framework whereby estrogen promotes greater rewarding effects of nicotine in females via enhanced dopamine release in the nucleus accumbens (NAcc). During withdrawal, we suggest that corticotropin-releasing factor (CRF) stress systems are sensitized and promote a greater suppression of dopamine release in the NAcc of females versus males. Taken together, females display enhanced nicotine reward via estrogen and amplified effects of withdrawal via stress systems. Although this framework focuses on sex differences in adult rats, it is also applied to adolescent females who display enhanced rewarding effects of nicotine, but reduced effects of withdrawal from this drug. Since females experience strong rewarding effects of nicotine, a clinical implication of our hypothesis is that specific strategies to prevent smoking initiation among females are critical. Also, anxiolytic medications may be more effective in females that experience intense stress during withdrawal. Furthermore, medications that target withdrawal should not be applied in a unilateral manner across age and sex, given that nicotine withdrawal is lower during adolescence. This review highlights key factors that promote nicotine use in females, and future studies on sex-dependent interactions of stress and reward systems are needed to test our mechanistic hypotheses. Future studies in this area will have important translational value toward reducing health disparities produced by nicotine use in females. PMID:23684991

  1. Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors

    PubMed Central

    Gold, Allison B.; Keller, Ashleigh B.; Perry, David C.

    2010-01-01

    We examined for immediate and persistent changes in nAChRs in cerebral cortex, thalamus and striatum of male rats caused by prenatal exposure to nicotine from gestational day 3 to postnatal day 10 (PN10), and how such exposure affected the responses of adolescents to subsequent nicotine challenge. Receptor numbers were assessed by [3H]epibatidine binding and receptor function was measured by acetylcholine-stimulated 86Rb efflux (cerebral cortex and thalamus) and nicotine-stimulated dopamine release (striatum). Immediate effects of prenatal nicotine, assessed in PN10 animals, were not detected for any parameter. A subsequent 14 day nicotine exposure in adolescence revealed persistent changes caused by prenatal nicotine exposure. Nicotine exposure in adolescents caused up-regulation of binding in all three regions; however, this up-regulation was lost in thalamus from animals prenatally exposed to nicotine. Nicotine exposure in adolescents caused decreased nicotine-stimulated dopamine release in striatum; this effect was also lost in animals prenatally exposed to nicotine. Comparison of parameters in PN10 and PN42 rats revealed developmental changes in the CNS cholinergic system. In thalamus, binding increased with age, as did the proportion of 86Rb efflux with high sensitivity to acetylcholine. In cortex, binding also increased with age, but there was no change in total 86Rb efflux, and the proportion of high to low sensitivity efflux declined with age. Nicotine-stimulated striatal dopamine release (both total and α-conotoxin MII-resistant release) increased with age in naïve animals, but not in those prenatally exposed to nicotine. These findings demonstrate that prenatal exposure to nicotine causes alterations in the regulation of nAChRs by nicotine that persist into adolescence. These changes may play a role in the increased risk for nicotine addiction observed in adolescent offspring of smoking mothers. PMID:19028470

  2. Substance Use, Abuse, and Dependency in Adolescence

    ERIC Educational Resources Information Center

    Lasser, Jon; Schmidt, Eric

    2009-01-01

    This article highlights the problem of substance use and abuse among adolescents and discusses the important role of school leaders in addressing this problem. Drug and alcohol use among adolescents is a significant and serious problem. In fact, an alarmingly high number of students report that they have used drugs or alcohol. Substance use and…

  3. Exploring the association of John Henry active coping and education on smoking behavior and nicotine dependence among Blacks in the USA.

    PubMed

    Fernander, Anita F; Patten, Christi A; Schroeder, Darrell R; Stevens, Susanna R; Eberman, Kay M; Hurt, Richard D

    2005-02-01

    Although smoking is used as a coping tool in response to stress and Blacks have been found to report smoking more in response to stress than Whites, little research exists that has examined ethno-culturally specific constructs of stress and coping as they relate to smoking behavior and nicotine dependence among Blacks in the USA. This study explored the association between the ethno-culturally interactively defined construct of John Henryism, as well as the individual contributions of John Henry active coping and education on smoking behavior and nicotine dependence in a relatively urban-Midwestern Black population. Self-identified Black patients (n = 146) who had previously received a clinical intervention for nicotine dependence were followed to assess smoking status and John Henry active coping. Results revealed that patients with low levels of education who had low levels of John Henry active coping reported higher nicotine dependence scores than any other education by John Henry active coping group. Furthermore, low levels of John Henry active coping were associated with the use of menthol cigarettes and lower-educational level was associated with smoking greater than 20 cigarettes per day. Further community-based studies examining this construct among Black smokers in various socio-cultural contexts are needed to clarify the association between John Henry active coping and socioeconomic status on smoking behavior and nicotine dependence among Blacks.

  4. Sex differences in nicotine dependence among addictions clients accessing a smoking cessation programme in Vancouver, British Columbia, Canada.

    PubMed

    Okoli, C T C; Torchalla, I; Khara, M

    2012-11-01

    Most individuals in drug treatment programmes use tobacco and are dependent on nicotine. For 323 participants (65% men, mean age = 49.3 years) with a history of substance use disorder (SUD) and/or psychiatric disorders (PD) enrolled in a tobacco dependence clinic programme, we compared baseline characteristics among women and men and examined factors associated with nicotine dependence (ND). Individuals with mood, anxiety and psychotic disorders were more likely to be female, whereas men were more likely to be characterized by alcohol, cocaine and marijuana use, older age, older age at smoking initiation and higher confidence in quitting smoking scores. In stratified multivariate analyses, among women, history of an anxiety disorder and a greater number of cigarettes smoked per day were associated with higher ND scores; among men, a greater number of cigarettes smoked per day and higher confidence in quitting scores were associated with higher ND scores. Given the differences in smoking, SUD and PD histories between women and men accessing addiction treatment, and differential associations with ND, it is important to further explore factors that may enhance tailored treatments and inform future studies examining biological and psychosocial factors for tobacco use in SUD and PD treatment populations.

  5. Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

    PubMed

    Gould, Thomas J; Wilkinson, Derek S; Yildirim, Emre; Poole, Rachel L F; Leach, Prescott T; Simmons, Steven J

    2014-03-01

    Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories.

  6. Baseline-dependent modulating effects of nicotine on voluntary and involuntary attention measured with brain event-related P3 potentials.

    PubMed

    Knott, Verner; Choueiry, Joelle; Dort, Heather; Smith, Dylan; Impey, Danielle; de la Salle, Sara; Philippe, Tristan

    2014-07-01

    Cholinergic stimulation produces cognitive effects that vary across individuals, and stimulus/task conditions. As of yet, the role of individual differences in moderating the effects of the nicotinic acetylcholine receptor agonist nicotine on specific attentional functions and their neural and behavioral correlates is not fully understood. In this randomized, double-blind, placebo-controlled study of 64 healthy non-smokers, we address the contribution of baseline-dependence to inter-individual variability in response to nicotine gum (6 mg) assessed with event-related brain potential (ERP) indices of involuntary (the anteriorly distributed P3a) and voluntary (the posteriorly distributed P3b) attention derived from an active 3-stimulus auditory oddball paradigm involving listening to standard and novel stimuli and detection and response to target stimuli. Nicotine enhanced the amplitude of P3a elicited during the processing of novel stimuli but only in individuals with relatively low baseline P3a amplitudes. Exhibiting an inverted-U nicotine response profile, target P3b and standard N1 amplitudes were increased and decreased in participants with low and high baseline amplitudes, respectively. In all, the findings corroborate the involvement of nicotinic mechanisms in attention, generally acting to increase attentional capacity in relatively low attentional functioning (reduced baseline ERPs) individuals, while having negative or detrimental effects in those with medium/high attentional levels (increased baseline ERPs), and in a manner that is differentially expressed during bottom-up (involuntary) attentional capture and top-down (voluntary) attentional allocation.

  7. Ferulic Acid modulates altered lipid profiles and prooxidant/antioxidant status in circulation during nicotine-induced toxicity: a dose-dependent study.

    PubMed

    Sudheer, Adluri Ram; Chandran, Kalpana; Marimuthu, Srinivasan; Menon, Venugopal Padmanabhan

    2005-01-01

    Nicotine, an active ingredient of tobacco smoke, is known to induce hyperlipidemia and disturb the prooxidant-antioxidant status. In our study, ferulic acid, a naturally occurring nutritional compound, was tested for its antioxidant and antihyperlipidemic property in a dose-dependent manner against nicotine-induced toxicity in female Wistar rats. We tested three different doses of ferulic acid-10 mg, 20 mg, and 40 mg/kg body weight-for their protective effects. The activities of biochemical marker enzymes lactate dehydrogenase and alkaline phosphatase, levels of peroxidative indices (thiobarbituric acid reactive substances and hydroperoxides), nitric oxide, and circulatory lipids (cholesterol, triglycerides, free fatty acids, and phospholipids) were increased significantly in the nicotine-treated group when compared to normal, which were brought down in ferulic acid-treated groups. The antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, vitamin E, and reduced glutathione) was found to be decreased in the nicotine-treated group, and was significantly increased in ferulic acid-administered groups. Further, ferulic acid also positively modulated the nicotine-induced changes in the micronutrients (zinc and copper) level. The dose 20 mg/kg body weight was found to be more effective than the other two doses. Our data suggest that FA exerts its preventive effects by modulating the degree of lipid peroxidation, antioxidant status, lipid profiles, and trace element levels during nicotine-induced toxicity. PMID:20021059

  8. E-cigarettes: Are we renormalizing public smoking? Reversing five decades of tobacco control and revitalizing nicotine dependency in children and youth in Canada

    PubMed Central

    Stanwick, Richard

    2015-01-01

    An electronic cigarette (e-cigarette) is a battery attached to a chamber containing liquid that may (or may not) contain nicotine. The battery heats the liquid and converts it into a vapour, which is inhaled, mimicking tobacco smoking. The e-cigarette does not rely on tobacco as a source of nicotine but, rather, vaporizes a liquid for inhalation. E-liquids are often flavoured and may contain nicotine in various concentrations, although actual amounts are seldom accurately reflected in container labelling. The deleterious effects of nicotine on paediatric health are well established. The use of e-cigarettes in the paediatric age group is on the rise in Canada, as are associated nicotine poisonings. E-devices generate substantial amounts of fine particulate matter, toxins and heavy metals at levels that can exceed those observed for conventional cigarettes. Children and youth are particularly susceptible to these atomized products. Action must be taken before these devices become a more established public health hazard. Policies to denormalize tobacco smoking in society and historic reductions in tobacco consumption may be undermined by this new ‘gateway’ product to nicotine dependency. PMID:25838785

  9. Inhalant Abuse and Dependence Among Adolescents in the United States

    PubMed Central

    WU, LI-TZY; PILOWSKY, DANIEL J.; SCHLENGER, WILLIAM E.

    2005-01-01

    Objective To examine the patterns of inhalant use and correlates of the progression from inhalant use to abuse and dependence among adolescents aged 12 to 17. Method Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Multinominal logistic regression was used to identify the characteristics associated with progression to inhalant abuse and dependence. Results Inhalant use was common among the studied adolescents. Among adolescents aged 12 to 17, 0.4% met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors. Conclusions Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youths with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school–age children. PMID:15381887

  10. Using Books to Prevent and Treat Adolescent Chemical Dependency.

    ERIC Educational Resources Information Center

    Pardeck, John T.

    1991-01-01

    Presents strategies for using bibliotherapeutic process to prevent and treat adolescent alcohol and drug abuse. Definitions, goals, and principles of bibliotherapy are overviewed. Synopses of several useful books that focus on chemical dependency are presented. (Author)

  11. Crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research

    PubMed Central

    Wen, L; Yang, Z; Cui, W; Li, M D

    2016-01-01

    Cigarette smoking is a leading cause of preventable death throughout the world. Nicotine, the primary addictive compound in tobacco, plays a vital role in the initiation and maintenance of its use. Nicotine exerts its pharmacological roles through nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels consisting of five membrane-spanning subunits. Besides the CHRNA4, CHRNB2 and CHRNA5/A3/B4 cluster on chromosome 15, which has been investigated intensively, recent evidence from both genome-wide association studies and candidate gene-based association studies has revealed the crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence (ND). These studies demonstrate two distinct loci within this region. The first one is tagged by rs13277254, upstream of the CHRNB3 gene, and the other is tagged by rs4952, a coding single nucleotide polymorphism in exon 5 of that gene. Functional studies by genetic manipulation in mice have shown that α6*-nAChRs, located in the ventral tegmental area (VTA), are of great importance in controlling nicotine self-administration. However, when the α6 subunit is selectively re-expressed in the VTA of the α6−/− mouse by a lentiviral vector, the reinforcing property of nicotine is restored. To further determine the role of α6*-nAChRs in the process of nicotine-induced reward and withdrawal, genetic knock-in strains have been examined, which showed that replacement of Leu with Ser in the 9′ residue in the M2 domain of α6 produces nicotine-hypersensitive mice (α6 L9′S) with enhanced dopamine release. Moreover, nicotine-induced upregulation may be another ingredient in the pathology of nicotine addiction although the effect of chronic nicotine exposure on the expression of α6-containing receptors is controversial. To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation

  12. Efficacy and Tolerability of Pharmacotherapies to Aid Smoking Cessation in Adolescents

    PubMed Central

    Bailey, Steffani R.; Crew, Erin E.; Riske, Emily C.; Ammerman, Seth; Robinson, Thomas N.; Killen, Joel D.

    2012-01-01

    Adolescent smoking remains a public health problem. Despite concerns regarding adolescent nicotine dependence, few well-designed smoking cessation studies have been conducted with teen smokers. This is particularly true regarding pharmacological treatments for nicotine dependence. Currently, pharmacological aids are not recommended for treating adolescent nicotine dependence, as efficacy has not been shown in this population. This review includes studies that have examined the efficacy of pharmacotherapy for smoking abstinence and/or reduction in cigarette consumption among adolescent smokers who want to quit smoking, lab-based adolescent studies that have examined the effectiveness of these medications in reducing cravings and/or withdrawal symptoms, and/or studies that have assessed the tolerability of medications for smoking cessation in adolescent smokers. This review provides information on the pharmacologic action of each medication, the efficacy of each medication for adolescent smoking cessation, the tolerability of each medication based on reported adverse events, and compliance with the medication protocols. Thirteen relevant articles were identified and included in the review. Nicotine patch, nicotine gum, nicotine nasal spray, bupropion, and varenicline have been studied in adolescent smokers. The adverse events reported in the studies on pharmacology for adolescent smoking suggest that the side effect profiles for nicotine replacement therapy, bupropion, and varenicline are similar to those reported in adult studies. There is some evidence of efficacy of nicotine patch and bupropion at end of treatment (efficacy of varenicline has not been assessed), but none of the medications included in this review were efficacious in promoting long-term smoking cessation among adolescent smokers. It is noted that many of the study protocols did not follow the recommended dose or length of pharmacotherapy for adults, rendering it difficult to determine the true

  13. Nicotine and sympathetic neurotransmission.

    PubMed

    Haass, M; Kübler, W

    1997-01-01

    Nicotine increases heart rate, myocardial contractility, and blood pressure. These nicotine-induced cardiovascular effects are mainly due to stimulation of sympathetic neurotransmission, as nicotine stimulates catecholamine release by an activation of nicotine acetylcholine receptors localized on peripheral postganglionic sympathetic nerve endings and the adrenal medulla. The nicotinic acetylcholine receptor is a ligand-gated cation channel with a pentameric structure and a central pore with a cation gate, which is essential for ion selectivity and permeability. Binding of nicotine to its extracellular binding site leads to a conformational change of the central pore, which results in the influx of sodium and calcium ions. The resulting depolarization of the sympathetic nerve ending stimulates calcium influx through voltage-dependent N-type calcium channels, which triggers the nicotine-evoked exocytotic catecholamine release. In the isolated perfused guinea-pig heart, cardiac energy depletion sensitizes cardiac sympathetic nerves to the norepinephrine-releasing effect of nicotine, as indicated by a leftward shift of the concentration-response curve, a potentiation of maximum transmitter release, and a delay of the tachyphylaxis of nicotine-evoked catecholamine release. This sensitization was also shown to occur in the human heart under in vitro conditions. Through the intracardiac release of norepinephrine, nicotine induces a beta-adrenoceptor-mediated increase in heart rate and contractility, and an alpha-adrenoceptor-mediated increase in coronary vasomotor tone. The resulting simultaneous increase in oxygen demand and coronary resistance has a detrimental effect on the oxygen balance of the heart, especially in patients with coronary artery disease. Sensitization of the ischemic heart to the norepinephrine-releasing effect of nicotine may be a trigger for acute cardiovascular events in humans, such as acute myocardial infarction and/or life

  14. Exercise as an adjunct to nicotine gum in treating tobacco dependence among women

    PubMed Central

    Kinnunen, Taru; Leeman, Robert F.; Korhonen, Tellervo; Terwal, Donna M.; Garvey, Arthur J.; Quiles, Zandra N.; Hartley, L. Howard

    2013-01-01

    This was the first randomized, controlled smoking cessation trial assessing the efficacy of an exercise intervention as an adjunct to nicotine gum therapy in comparison to both equal contact control and standard care control conditions. Sedentary female smokers aged 18-55 were provided with nicotine gum treatment along with brief behavioral counseling and were randomized into one of these three behavioral adjunct conditions. In the “intent-to-treat” sample (N=182), at end of treatment and at one-year follow up, there were clear, but non-significant, trends in univariate analyses in which the exercise and equal contact control conditions both had higher rates of abstinence than the standard care control. However, when adjusting for other predictors of relapse in a multiple logistic regression, both exercise and equal contact control showed an advantage over standard care control in avoiding early relapse (i.e., after 1 week). In a multivariate survival model adjusting for other predictors, the equal contact condition had a significantly lower likelihood of relapse compared to the standard care condition and there was a near significant trend in which exercise offered an advantage over standard care as well. While these findings suggest a slightly improved likelihood of abstinence with exercise compared with standard care, exercise did not differ from equal contact control in its efficacy. Potential explanations for these equivalent levels of efficacy and implications for the findings are discussed. PMID:18418791

  15. Circadian dosing time dependency in the forearm skin penetration of methyl and hexyl nicotinate.

    PubMed

    Reinberg, A E; Soudant, E; Koulbanis, C; Bazin, R; Nicolaï, A; Mechkouri, M; Touitou, Y

    1995-01-01

    The forearm skin penetration of hydrophilic methyl nicotinate (MN) and lipophilic hexyl nicotinate (HN) was assessed around the clock. The sixteen healthy women (median age: 22 years, weight: 57 kg and height: 162 cm) who volunteered for the study were synchronized with a diurnal activity from 07.00h (+/- 1h) to 23.00h (+/- 1h.30min) and a nocturnal rest before and during the 48h sojourn in air-conditioned rooms (26 degrees C +/- 0.5 degrees C). Both HN (0.5% ethanol solution) and MN (5% ethanol solution) have a vasodilative effect on dermal vessels. The lag time (LT) between the delivery of a fixed volume (10 microliters) of the agent at the skin surface and the beginning of the vasodilatation, detected with a laser-Doppler method, was used to quantify the penetration kinetics. Tests were performed every 4h, at fixed clock hours, over a span of a 40h. Two types of tests were done with each of the agents: fixed site (one site only) and shifted sites (10 different places). Both cosinor and ANOVA have been used for statistical analyses. The shortest LT (fastest penetration) was located around 04.00h. The longest LT (slowest penetration) occurred during the day with a single peak around 13.00h in three of the situations, or two peaks (HN with fixed site). A rather large rhythm amplitude (peak-to-trough difference larger than 50% of the 24h mean LT) was validated.

  16. Subchronic nicotine exposure in adolescence induces long-term effects on hippocampal and striatal cannabinoid-CB1 and mu-opioid receptors in rats.

    PubMed

    Marco, Eva M; Granstrem, Oleg; Moreno, Enrique; Llorente, Ricardo; Adriani, Walter; Laviola, Giovanni; Viveros, Maria-Paz

    2007-02-14

    There is evidence for the existence of functional interactions between nicotine and cannabinoids and opioid compounds in adult experimental animals. However, there is scarce information about these relationships in young animals. In the present study we evaluated short and long-term effects of a subchronic nicotine treatment [0.4 mg/kg daily i.p. injections from postnatal day (PND) 34 to PND 43], upon hippocampal and striatal cannabinoid-CB(1) and mu-opioid receptors in Wistar rats of both genders. Rats were sacrificed 2 h after the last nicotine injection (short-term effects, PND 43) or one month later (long-term effects, PND 75). Hippocampal and striatal cannabinoid CB(1) and mu-opioid receptors were quantified by Western blotting. The subchronic nicotine treatment induced a region-dependent long-lasting effect in cannabinoid CB(1) receptor: a significant increase in hippocampal cannabinoid CB(1) receptors and a significant decrease in striatal cannabinoid CB(1) receptors, with these effects being similar in males and females. With respect to mu-opioid receptors, subchronic nicotine induced a significant down-regulation in hippocampal and striatal mu-opioid receptors in the long-term, and within the striatum the effects were more marked in adult males than in females. The present results indicate that juvenile nicotine taking may have implications for the endocannabinoid and endogenous opioid function and for the behaviors served by those systems, this includes possible modification of the response of adults to different psychotropic drugs, i.e. cannabis and morphine/heroin when taken later in life.

  17. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  18. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder.

  19. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  20. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder.

  1. The Hardening Hypothesis: Is the Ability to Quit Decreasing Due to Increasing Nicotine Dependence? A Review and Commentary

    PubMed Central

    Hughes, John R.

    2011-01-01

    The “hardening hypothesis” states tobacco control activities have mostly influenced those smokers who found it easier to quit and, thus, remaining smokers are those who are less likely to stop smoking. This paper first describes a conceptual model for hardening. Then the paper describes important methodological distinctions (quit attempts vs. ability to remain abstinent as indicators, measures of hardening per se vs. measures of causes of hardening, and dependence measures that do vs. do not include cigarettes per day (cigs/day).) After this commentary, the paper reviews data from prior reviews and new searches for studies on one type of hardening: the decreasing ability to quit due to increasing nicotine dependence. Overall, all four studies of the general population of smokers found no evidence of decreased ability to quit; however, both secondary analyses of treatment-seeking smokers found quit rates were decreasing over time. Cigs/day and time-to-first cigarette measures of dependence did not increase over time; however, two studies found that DSM-defined dependence appeared to be increasing over time. Although these data suggest hardening may be occurring in treatment seekers but perhaps not in the general population of smokers, this conclusion may be premature given the small number of data sets and indirect measures of quit success and dependence in the data sets. Future studies should include questions about quit attempts, ability to abstain, treatment use, and multi-item dependence measures. PMID:21411244

  2. The hardening hypothesis: is the ability to quit decreasing due to increasing nicotine dependence? A review and commentary.

    PubMed

    Hughes, John R

    2011-09-01

    The "hardening hypothesis" states tobacco control activities have mostly influenced those smokers who found it easier to quit and, thus, remaining smokers are those who are less likely to stop smoking. This paper first describes a conceptual model for hardening. Then the paper describes important methodological distinctions (quit attempts vs. ability to remain abstinent as indicators, measures of hardening per se vs. measures of causes of hardening, and dependence measures that do vs. do not include cigarettes per day (cigs/day).) After this commentary, the paper reviews data from prior reviews and new searches for studies on one type of hardening: the decreasing ability to quit due to increasing nicotine dependence. Overall, all four studies of the general population of smokers found no evidence of decreased ability to quit; however, both secondary analyses of treatment-seeking smokers found quit rates were decreasing over time. Cigs/day and time-to-first cigarette measures of dependence did not increase over time; however, two studies found that DSM-defined dependence appeared to be increasing over time. Although these data suggest hardening may be occurring in treatment seekers but not in the general population of smokers, this conclusion may be premature given the small number of data sets and indirect measures of quit success and dependence in the data sets. Future studies should include questions about quit attempts, ability to abstain, treatment use, and multi-item dependence measures.

  3. Nicotine elicits methamphetamine-seeking in rats previously administered nicotine.

    PubMed

    Neugebauer, N M; Harrod, S B; Bardo, M T

    2010-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior.

  4. Inhalant Use, Abuse, and Dependence among Adolescent Patients: Commonly Comorbid Problems.

    ERIC Educational Resources Information Center

    Sakai, Joseph T.; Hall, Shannon K.; Mikulich-Gilbertson, Susan K.; Crowley, Thomas J.

    2004-01-01

    Objective: Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol…

  5. Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking.

    PubMed

    Gamaleddin, Islam; Wertheim, Carrie; Zhu, Andy Z X; Coen, Kathleen M; Vemuri, Kiran; Makryannis, Alex; Goldberg, Steven R; Le Foll, Bernard

    2012-01-01

    The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine-seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self-administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212-2, a CB1/2 agonist, on intravenous nicotine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212-2 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212-2 on nicotine- and cue-induced reinstatement of nicotine seeking were also studied, as well as the effects of WIN 55,212-2 on nicotine discrimination. WIN 55,212-2 decreased nicotine self-administration under the FR schedule. However, co-administration of WIN 55,212-2 with nicotine decreased responding for food, which suggests that this effect was non-selective. In contrast, WIN 55,212-2 increased both nicotine self-administration and responding for food under the PR schedule, produced dose-dependent reinstatement of nicotine seeking, and enhanced the reinstatement effects of nicotine-associated cues. Some of these effects were reversed by the CB1 antagonist rimonabant, but not by the CB2 antagonist AM630. In the drug discrimination tests between saline and 0.4 mg/kg nicotine, WIN 55,212-2 produced no nicotine-like discriminative effects but significantly potentiated discriminative stimulus effects of nicotine at the low dose through a CB1-receptor-dependent mechanism. These findings indicate that cannabinoid CB1-receptor stimulation increases the reinforcing effects of nicotine and precipitates relapse to nicotine-seeking behaviour in abstinent subjects. Thus, modulating CB1-receptor signalling might have therapeutic value for treating nicotine dependence. PMID:21521420

  6. The Risk of Suicide according to Drug Abuse and Nicotine Dependence in Patients with War Injuries and Chronic Traumatic Stress Disorder

    PubMed Central

    Ghaffari Nejad, Alireza; Kheradmand, Ali; Mirzaiee, Mahdieh

    2011-01-01

    Background The incidence of suicide is higher in individuals with post-traumatic stress disorder (PTSD) than the general population. This prevalence rate is related to many factors including drug dependence. This study was conducted in people wounded during the Iran-Iraq war with PTSD, in order to compare the risk of suicide in those with and without drug and nicotine dependence. Methods This cross-sectional study, conducted in 2007-2008, comprised 104 male individuals who had participated in the Iran-Iraq war and had a current diagnosis of PTSD. They had been referred to a psychiatry hospital and the psychiatrists' offices in Kerman, Iran. Three questionnaires were used including Davidson Trauma Scale, California Risk Estimator for Suicide and the Fagerstrom Test for Nicotine Dependence to assess the severity of PTSD, the risk of suicide, and nicotine dependence, respectively. Data were analyzed by descriptive and analytical statistics using chi-square, regression, analysis of variance (ANOVA), student-t and correlation tests. Findings The severity of PTSD was significantly different in individuals with low to moderate dependence on cigarette smoking than in those with heavy dependence on smoking (P = 0.002). However, the corresponding figures were not significantly different in individuals with and without substance abuse. Although the risk of suicide had no significant difference among individuals with low to moderate dependence on cigarettes compared to those with high nicotine dependence, it was higher in subjects with substance abuse than in those without it (P = 0.0001). Conclusion Our findings suggest that dependence on cigarettes may not play a role in increasing the risk of suicide, whereas the dependence on opium and its derivatives may increase this risk. Therefore, prevention and treatment of drug abuse may be effective on the incidence of suicide in patients with war injuries and PTSD. PMID:24494115

  7. Genome-Wide Association Study of Nicotine Dependence in American Populations: Identification of Novel Risk Loci in Both African-Americans and European-Americans

    PubMed Central

    Gelernter, Joel; Kranzler, Henry R.; Sherva, Richard; Almasy, Laura; Herman, Aryeh I.; Koesterer, Ryan; Zhao, Hongyu; Farrer, Lindsay A.

    2015-01-01

    BACKGROUND We report a genome-wide association study (GWAS) of nicotine dependence defined on the basis of scores on the Fagerström Test for Nicotine Dependence in European-American (EA) and African-American (AA) populations. METHODS Our sample, from the one used in our previous GWAS, included only subjects who had smoked >100 cigarettes lifetime (2114 EA and 2602 AA subjects) and an additional 927 AA and 2003 EA subjects from the Study of Addiction: Genetics and Environment project [via the database of Genotypes and Phenotypes (dbGAP)]. GWAS analysis considered Fagerström Test for Nicotine Dependence score as an ordinal trait, separately in each population and sample and by combining the results in meta-analysis. We also conducted analyses that were adjusted for other substance use disorder criteria in a single nucleotide polymorphism (SNP) subset. RESULTS In EAs, one chromosome 7 intergenic region was genome-wide significant (GWS): rs13225753, p = 3.48 × 10−8 (adjusted). In AAs, GWS associations were observed at numerous SNPs mapped to a region on chromosome 14 of >305,000 base pairs (minimal p = 4.74 × 10−10). Two chromosome 8 regions were associated: p = 4.45 × 10−8 at DLC1 SNP rs289519 (unadjusted) and p = 1.10 × 10−9 at rs6996964 (adjusted for other substances), located between CSGALNACT1 and INTS10. No GWS associations were observed at the chromosome 15 nicotinic receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) previously associated with nicotine dependence and smoking quantity traits. TSNAX-DISC1 SNP rs821722 (p = 1.46 × 10−7) was the most significant result with substantial contributions from both populations; we previously identified DISC1 associations with opioid dependence. Pathway analysis identified association with nitric oxide synthase and adenosine monophosphate-activated protein kinase pathways in EAs. CONCLUSIONS The key risk loci identified, which require replication, offer novel insights into nicotine dependence biology. PMID

  8. Nicotinic acid– and monomethyl fumarate–induced flushing involves GPR109A expressed by keratinocytes and COX-2–dependent prostanoid formation in mice

    PubMed Central

    Hanson, Julien; Gille, Andreas; Zwykiel, Sabrina; Lukasova, Martina; Clausen, Björn E.; Ahmed, Kashan; Tunaru, Sorin; Wirth, Angela; Offermanns, Stefan

    2010-01-01

    The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein–coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of monomethyl fumarate. Here we analyzed the mechanisms underlying GPR109A-mediated flushing and show that both Langerhans cells and keratinocytes express GPR109A in mice. Using cell ablation approaches and transgenic cell type–specific GPR109A expression in Gpr109a–/– mice, we have provided evidence that the early phase of flushing depends on GPR109A expressed on Langerhans cells, whereas the late phase is mediated by GPR109A expressed on keratinocytes. Interestingly, the first phase of flushing was blocked by a selective cyclooxygenase-1 (COX-1) inhibitor, and the late phase was sensitive to a selective COX-2 inhibitor. Both monomethyl fumarate and nicotinic acid induced PGE2 formation in isolated keratinocytes through activation of GPR109A and COX-2. Thus, the early and late phases of the GPR109A-mediated cutaneous flushing reaction involve different epidermal cell types and prostanoid-forming enzymes. These data will help to guide new efficient approaches to mitigate nicotinic acid–induced flushing and may help to exploit the potential antipsoriatic effects of GPR109A agonists in the skin. PMID:20664170

  9. The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies

    PubMed Central

    Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

    2014-01-01

    BACKGROUND AND PURPOSE Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. EXPERIMENTAL APPROACHES To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. KEY RESULTS BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. CONCLUSION AND IMPLICATIONS Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. PMID:24750073

  10. Worms clear the smoke surrounding nicotine addiction.

    PubMed

    Kelley, Ann E

    2006-11-01

    In this issue of Cell, Feng et al. report a worm model of nicotine dependence that shows behavioral adaptations surprisingly similar to those in humans. These authors show a critical link between nicotinic receptors and TRP channels, which may represent a new therapeutic target for treating nicotine addiction.

  11. Reduction of Aggressive Episodes after Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Van Schalkwyk, Gerrit I.; Lewis, Alan S.; Qayyum, Zheala; Koslosky, Kourtney; Picciotto, Marina R.; Volkmar, Fred R.

    2015-01-01

    Aggression remains a major cause of morbidity in patients with autism spectrum disorder (ASD). Current pharmacotherapy for aggression is not always effective and is often associated with morbidity. Nicotinic acetylcholinergic neurotransmission may play a prominent role in ASD pathophysiology based on human and animal studies, and preclinical…

  12. The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

    PubMed

    Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J

    2015-12-30

    Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving.

  13. Genetics of nicotinic acetylcholine receptors: relevance to nicotine addiction

    PubMed Central

    Mineur, Yann S.; Picciotto, Marina R.

    2008-01-01

    Human twin studies have suggested that there is a substantial genetic component underlying nicotine dependence, ongoing smoking and ability to quit. Similarly, animal studies have identified a number of genes and gene products that are critical for behaviors related to nicotine addiction. Classical genetic approaches, gene association studies and genetic engineering techniques have been used to identify the gene products involved in nicotine dependence. One class of genes involved in nicotine-related behavior is the family of nicotinic acetylcholine receptors (nAChRs). These receptors are the primary targets for nicotine in the brain. Genetic engineering studies in mice have identified a number of subunits that are critical for the ability of nicotine to activate the reward system in the brain, consisting of the dopaminergic cell bodies in the ventral tegmental area and their terminals in the nucleus accumbens and other portions of the mesolimbic system. In this review we will discuss the various lines of evidence suggesting that nAChRs may be involved in smoking behavior, and will review the human and animal studies that have been performed to date examining the genetic basis for nicotine dependence and smoking. PMID:17632086

  14. The neuroeconomics of nicotine dependence: a preliminary functional magnetic resonance imaging study of delay discounting of monetary and cigarette rewards in smokers.

    PubMed

    MacKillop, James; Amlung, Michael T; Wier, Lauren M; David, Sean P; Ray, Lara A; Bickel, Warren K; Sweet, Lawrence H

    2012-04-30

    Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence.

  15. Discriminative and reinforcing stimulus effects of nicotine, cocaine, and cocaine + nicotine combinations in rhesus monkeys.

    PubMed

    Mello, Nancy K; Newman, Jennifer L

    2011-06-01

    Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was twofold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine's discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

  16. Nicotine replacement therapy

    MedlinePlus

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11: ...

  17. Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

    PubMed Central

    Torres, Oscar V.; Pipkin, Joseph A.; Ferree, Patrick; Carcoba, Luis M.

    2015-01-01

    Introduction: Previous work led to our hypothesis that sex differences produced by nicotine withdrawal are modulated by stress and dopamine systems in the nucleus accumbens (NAcc). We investigated our hypothesis by studying intact females to determine whether the mechanisms that promote withdrawal are ovarian-hormone mediated. Methods: Female rats were ovariectomized (OVX) or received sham surgery (intact) on postnatal day (PND 45–46). On PND 60, they received sham surgery (controls) or were prepared with nicotine pumps. Fourteen days later, half of the rats had their pumps removed (nicotine withdrawal) and the other half received sham surgery (nicotine exposure). Twenty-four hours later, the rats were tested for anxiety-like behavior using the elevated plus maze and light/dark transfer procedures. The NAcc was then dissected for analysis of several genes related to stress (CRF, UCN, CRF-R1, CRF-R2, CRF-BP, and Arrb2) or receptors for dopamine (Drd1 and Drd2) and estradiol (Esr2). Results: During withdrawal, intact females displayed an increase in anxiety-like behavior in both tests and CRF, UCN, and Drd1 gene expression. During nicotine exposure, intact females displayed a decrease in CRF-R1, CRF-R2, Drd3, and Esr2 gene expression and an increase in CRF-BP. This pattern of results was absent in OVX females. Conclusions: Nicotine withdrawal produced an increase in anxiety-like behavior and stress-associated genes in intact females that is distinct from changes produced by nicotine exposure. The latter effects were absent in OVX females, suggesting that stress produced by withdrawal is ovarian-hormone mediated. These findings have important implications towards understanding tobacco use liability among females. PMID:25762751

  18. New Developments in Understanding and Treating Adolescent Marijuana Dependence1

    PubMed Central

    Gray, Kevin M.

    2014-01-01

    Background Marijuana is the most commonly used illicit substance in the United States and worldwide. Marijuana use is a problem of increasing magnitude among adolescents. Use typically begins in adolescence and is associated with a variety of adverse outcomes. Method This article will present an overview of trends in marijuana use, and will review the endocannabinoid system and marijuana. It will discuss recent policy developments in US and their implications, especially for adolescents. Existing treatments will be reviewed, including findings from a recent randomized double-blind trial of N-acetylcysteine, a compound that reverses the dysregulation of the glutamate system that occurs in substance dependence. Conclusions The core treatment approaches include psychosocial interventions, sometimes in combination with each other. While a reduction in days of use is often achieved with most of these approaches, abstinence is a much more elusive goal. The evidence base for effective treatments remains inadequate especially with regard to adolescents, and there is an urgent need for more research in this area. Promising new treatments include N-acetylcysteine in conjunction with contingency management. PMID:25289370

  19. Nicotine Withdrawal

    PubMed Central

    McLaughlin, Ian; Dani, John A.; De Biasi, Mariella

    2015-01-01

    An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction. PMID:25638335

  20. Does Proximity Matter? Distance Dependence of Adolescent Friendships

    PubMed Central

    Preciado, Paulina; Snijders, Tom A.B.; Burk, William J.; Stattin, Håkan; Kerr, Margaret

    2014-01-01

    Geographic proximity is a determinant factor of friendship. Friendship datasets that include detailed geographic information are scarce, and when this information is available, the dependence of friendship on distance is often modelled by pre-specified parametric functions or derived from theory without further empirical assessment. This paper aims to give a detailed representation of the association between distance and the likelihood of friendship existence and friendship dynamics, and how this is modified by a few basic social and individual factors. The data employed is a three-wave network of 336 adolescents living in a small Swedish town, for whom information has been collected on their household locations. The analysis is a three-step process that combines 1) nonparametric logistic regressions to unravel the overall functional form of the dependence of friendship on distance, without assuming it has a particular strength or shape; 2) parametric logistic regressions to construct suitable transformations of distance that can be employed in 3) stochastic models for longitudinal network data, to assess how distance, individual covariates, and network structure shape adolescent friendship dynamics. It was found that the log-odds of friendship existence and friendship dynamics decrease smoothly with the logarithm of distance. For adolescents in different schools the dependence is linear, and stronger than for adolescents in the same school. Living nearby accounts, in this dataset, for an aspect of friendship dynamics that is not explicitly modelled by network structure or by individual covariates. In particular, the estimated distance effect is not correlated with reciprocity or transitivity effects. PMID:25530664

  1. The effectiveness of nicotine patch and nicotine lozenge in very heavy smokers.

    PubMed

    Shiffman, Saul; Di Marino, Michael E; Pillitteri, Janine L

    2005-01-01

    The efficacy of nicotine replacement therapy (NRT) among very heavy and highly dependent smokers was examined in a secondary analysis of two randomized clinical trials of NRT. In the first trial, smokers were assigned to active patch (n=249) or placebo (n=253) plus intensive behavioral treatment. In the second trial, smokers were assigned to active 4-mg nicotine lozenge (n=450) or placebo (n=451) plus brief behavioral treatment. Nicotine patch and lozenge significantly increased 6-month continuous abstinence quit rates in both very heavy (>or=40 cigarettes per day) and highly dependent (Fagerström Tolerance Questionnaire or Fagerström Test for Nicotine Dependence score >7) smokers. The effect of active NRT treatment did not differ significantly by smoking rate or nicotine dependence, with the exception that the nicotine patch was significantly more effective than placebo in highly dependent smokers. The nicotine patch and lozenge are effective (vs. placebo) even in heavy and highly dependent smokers. PMID:15723732

  2. Prospective Assessment of Cannabis Withdrawal in Adolescents with Cannabis Dependence: A Pilot Study

    ERIC Educational Resources Information Center

    Milin, Robert; Manion, Ian; Dare, Glenda; Walker, Selena

    2008-01-01

    A study to identify and assess the withdrawal symptoms in adolescents afflicted with cannabis dependence is conducted. Results conclude that withdrawal symptoms of cannabis were present in adolescents seeking treatment for this substance abuse.

  3. Nicotine-mediated invasion and migration of non-small cell lung carcinoma cells by modulating STMN3 and GSPT1 genes in an ID1-dependent manner

    PubMed Central

    2014-01-01

    Background Inhibitor of DNA binding/Differentiation 1 (ID1) is a helix loop helix transcription factor that lacks the basic DNA binding domain. Over-expression of ID1 has been correlated with a variety of human cancers; our earlier studies had shown that reported ID1 is induced by nicotine or EGF stimulation of non-small cell lung cancer (NSCLC) cells and its down regulation abrogates cell proliferation, invasion and migration. Here we made attempts to identify downstream targets of ID1 that mediate these effects. Methods A microarray analysis was done on two different NSCLC cell lines (A549 and H1650) that were transfected with a siRNA to ID1 or a control, non-targeting siRNA. Cells were stimulated with nicotine and genes that were differentially expressed upon nicotine stimulation and ID1 depletion were analyzed to identify potential downstream targets of ID1. The prospective role of the identified genes was validated by RT-PCR. Additional functional assays were conducted to assess the role of these genes in nicotine induced proliferation, invasion and migration. Experiments were also conducted to elucidate the role of ID1, which does not bind to DNA directly, affects the expression of these genes at transcriptional level. Results A microarray analysis showed multiple genes are affected by the depletion of ID1; we focused on two of them: Stathmin-like3 (STMN3), a microtubule destabilizing protein, and GSPT1, a protein involved in translation termination; these proteins were induced by both nicotine and EGF in an ID1 dependent fashion. Overexpression of ID1 in two different cell lines induced STMN3 and GSPT1 at the transcriptional level, while depletion of ID1 reduced their expression. STMN3 and GSPT1 were found to facilitate the proliferation, invasion and migration of NSCLC cells in response to nAChR activation. Attempts made to assess how ID1, which is a transcriptional repressor, induces these genes showed that ID1 down regulates the expression of two

  4. Nicotine alters lung branching morphogenesis through the alpha7 nicotinic acetylcholine receptor.

    PubMed

    Wongtrakool, Cherry; Roser-Page, Susanne; Rivera, Hilda N; Roman, Jesse

    2007-09-01

    There is abundant epidemiological data linking prenatal environmental tobacco smoke with childhood asthma and wheezing, but the underlying molecular and physiological mechanisms that occur in utero to explain this link remain unelucidated. Several studies suggest that nicotine, which traverses the placenta, is a causative agent. Therefore, we studied the effects of nicotine on lung branching morphogenesis using embryonic murine lung explants. We found that the expression of alpha(7) nicotinic acetylcholine receptors, which mediate many of the biological effects of nicotine, is highest in pseudoglandular stage lungs compared with lungs at later stages. We then studied the effects of nicotine in the explant model and found that nicotine stimulated lung branching in a dose-dependent fashion. alpha-Bungarotoxin, an antagonist of alpha(7) nicotinic acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS-21, a specific agonist, stimulated branching, thereby mimicking the effects of nicotine. Explants deficient in alpha(7) nicotinic acetylcholine receptors did not respond to nicotine. Nicotine also stimulated the growth of the explant. Altogether, these studies suggest that nicotine stimulates lung branching morphogenesis through alpha(7) nicotinic acetylcholine receptors and may contribute to dysanaptic lung growth, which in turn may predispose the host to airway disease in the postnatal period.

  5. Chronic neonatal nicotine exposure increases excitation in the young adult rat hippocampus in a sex-dependent manner

    PubMed Central

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2012-01-01

    Smoking during pregnancy exposes the fetus to nicotine, resulting in nicotine-stimulated neurotransmitter release. Recent evidence suggests that the hippocampus develops differently in males and females with delayed maturation in males. We show that chronic nicotine exposure during the first postnatal week has sex-specific long-term effects. Neonatal rat pups were chronically treated with nicotine (6 mg/kg/day) (CNN) from postnatal day 1 to 7 or milk only (Controls), and hippocampal slices were prepared from Control- and CNN-treated young adults. Field excitatory postsynaptic potentials (fEPSPs) or population spikes (PSs) were recorded from the CA1 hippocampus following CA1 s. radiatum stimulation. Input/Output curves constructed from fEPSP data indicated that CNN-males, but not females, had significantly increased excitatory responses compared to Controls (p<0.05, n=10 Con, n=11 CNN). Long-term potentiation (LTP) was not significantly changed by CNN. In the presence of bicuculline, which blocks inhibitory GABAA receptors, an epileptiform burst consisting of a series of PSs was evoked. The amplitude of the first PS was significantly larger in CNN-males and females compared to Controls (males: p<0.01, n=8 Con, n=8 CNN; females: p<0.05, n=9 Con, n=7 CNN). Only CNN-males also had significantly larger second PSs (p<0.05, n=8 con, n=8 CNN). Epileptiform activity evoked by zero Mg2+ incubation did not differ in amplitude or duration of bursts in CNN-males or females compared to Controls. These data indicate that neonatal nicotine exposure has long lasting effects and results in increased excitation within the CA1 hippocampus in adulthood, with males showing increased sensitivity to nicotine's effects. PMID:22119395

  6. Calcium-dependent effect of the thymic polypeptide thymopoietin on the desensitization of the nicotinic acetylcholine receptor

    SciTech Connect

    Revah, F.; Mulle, C.; Pinset, C.; Audhya, T.; Goldstein, G.; Changeux, J.P.

    1987-05-01

    The effects of the thymic polypeptide thymopoietin (Tpo) on the properties of the nicotinic acetylcholine receptor (AcChoR) were investigated by patch clamp techniques on mouse C/sub 2/ myotubes and by biochemical assays on AcChoR-rich membrane fragments purified from the Torpedo marmorata electric organ. At high concentrations (> 100 nM), Tpo inhibits the binding of cholinergic agonists to the AcChoR in a Ca/sup 2 +/-insensitive manner. At lower concentrations (2 nM), Tpo applied on C/sub 2/ myotubes simultaneously with nondesensitizing concentrations of acetylcholine results in the appearance of long closed times separating groups of openings. This effect depends on the presence of Ca/sup 2 +/ in the external medium. Outside-out recordings, performed with various concentrations of EGTA in the intracellular medium, suggest that Ca/sup 2 +/ acts on the cytoplasmic face of the membrane after entry through acetylcholine-activated channels. Parallel studies with T. marmorata AcChoR-rich membranes show that in the presence of Ca/sup 2 +/ Tpo causes a decrease in the apparent equilibrium dissociation constant of the noncompetitive blocker (/sup 3/H)phencyclidine, enhances, at low concentrations, the binding of (/sup 3/H)acetylcholine, and also alters the binding kinetics of the fluorescent agonist 6-(5-dimethylamino-1-naphthalenesulfonamido)-n-hexanoic acid ..beta..-(N-trimethylammonium bromide) ethyl ester to the AcChoR. It was concluded that, in the presence of Ca/sup 2 +/, Tpo displaces the conformational equilibrium of the AcChoR towards a high-affinity desensitized state and increases the transition rate towards the same state.

  7. Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African-American populations.

    PubMed

    Li, Ming D; Mangold, Jamie E; Seneviratne, Chamindi; Chen, Guo-Bo; Ma, Jennie Z; Lou, Xiang-Yang; Payne, Thomas J

    2009-01-01

    Previous studies have demonstrated that the gamma-aminobutyric acid type B (GABA(B)) receptor plays an essential role in modulating neurotransmitter release and regulating the activity of ion channels and adenyl cyclase. However, whether the naturally occurring polymorphisms in the two GABA(B) receptor subunit genes interact with each other to alter susceptibility to nicotine dependence (ND) remains largely unknown. In this study, we genotyped 5 and 33 single nucleotide polymorphisms (SNPs) for GABA(B) receptor subunit 1 and 2 genes (GABBR1, GABBR2), respectively, in a sample of 2037 individuals from 602 nuclear families of African- American (AA) or European-American (EA) origin. We conducted association analyses to determine (1) the association of each subunit gene with ND at both the individual SNP and haplotype levels and (2) the collective effect(s) of SNPs in both GABA(B) subunits on the development of ND. Several individual SNPs and haplotypes in GABBR2 were significantly associated with ND in both ethnic samples. Two haplotypes in AAs and one haplotype in EAs showed a protective effect against ND, whilst two other haplotypes in AAs and three haplotypes in EAs showed a risk effect for developing ND. Interestingly, these significant haplotypes were confined to two regions of GABBR2 in the AA and EA samples. Additionally, we found two minor haplotypes in GABBR1 to be positively associated with Heaviness of Smoking Index (HSI) in the EA sample. Finally, we demonstrated the presence of epistasis between GABBR1 and GABBR2 for developing ND. The variants of GABBR1 and GABBR2 are significantly associated with ND, and the involvement of GABBR1 is most likely through its interaction with GABBR2, whereas GABBR2 polymorphisms directly alter susceptibility to ND. Future studies are needed with more dense SNP coverage of GABBR1 and GABBR2 to verify the epistatic effects of the two subunit genes. PMID:19763258

  8. Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

    NASA Astrophysics Data System (ADS)

    Tapper, Andrew R.; McKinney, Sheri L.; Nashmi, Raad; Schwarz, Johannes; Deshpande, Purnima; Labarca, Cesar; Whiteaker, Paul; Marks, Michael J.; Collins, Allan C.; Lester, Henry A.

    2004-11-01

    The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with α4 nicotinic subunits containing a single point mutation, Leu9' --> Ala9' in the pore-forming M2 domain, rendering α4* receptors hypersensitive to nicotine. Selective activation of α4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of α4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.

  9. Nicotine Gum

    MedlinePlus

    ... program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine gum is in a ... at room temperature and away from light, excess heat and moisture (not in the bathroom). Throw away ...

  10. Measurement of Multiple Nicotine Dependence Domains Among Cigarette, Non-cigarette and Poly-tobacco Users: Insights from Item Response Theory*

    PubMed Central

    Strong, David R; Messer, Karen; Hartman, Sheri J.; Conway, Kevin P.; Hoffman, Allison; Pharris-Ciurej, Nikolas; White, Martha; Green, Victoria R.; Compton, Wilson M.; Pierce, John

    2015-01-01

    Background Nicotine dependence (ND) is a key construct that organizes physiological and behavioral symptoms associated with persistent nicotine intake. Measurement of ND has focused primarily on cigarette smokers. Thus, validation of brief instruments that apply to a broad spectrum of tobacco product users is needed. Methods We examined multiple domains of ND in a longitudinal national study of the United States population, the United States National Epidemiological Survey of Alcohol and Related Conditions (NESARC). We used methods based in item response theory to identify and validate increasingly brief measures of ND that included symptoms to assess ND similarly among cigarette, cigar, smokeless, and poly tobacco users. Results Confirmatory factor analytic models supported a single, primary dimension underlying symptoms of ND across tobacco use groups. Differential Item Functioning (DIF) analysis generated little support for systematic differences in response to symptoms of ND across tobacco use groups. We established significant concurrent and predictive validity of brief 3- and 5- symptom indices for measuring ND. Conclusions Measuring ND across tobacco use groups with a common set of symptoms facilitates evaluation of tobacco use in an evolving marketplace of tobacco and nicotine products. PMID:26005043

  11. A Practical Clinical Approach to the Treatment of Nicotine Dependence in Adolescents

    ERIC Educational Resources Information Center

    Upadhyaya, Himanshu; Deas, Deborah; Brady, Kathleen

    2005-01-01

    Cigarette smoking in the United States is predominantly a pediatric disorder and causes significant morbidity and mortality; tobacco is related to more than 400,000 deaths in the United States annually. Psychiatric comorbidity is associated with smoking, and early-onset smoking (before age 13) is robustly associated with psychopathology later in…

  12. Earlier violent television exposure and later drug dependence.

    PubMed

    Brook, David W; Saar, Naomi S; Brook, Judith S

    2008-01-01

    This research examined the longitudinal pathways from earlier violent television exposure to later drug dependence. African American and Puerto Rican adolescents were interviewed during three points in time (n = 463). Exposure to violent television programs in late adolescence predicted exposure to violent television programs in young adulthood, which in turn was related to tobacco/marijuana use, nicotine dependence, and later drug dependence. Some policy and clinical implications suggest regulating the times when violent television programs are broadcast, creating developmentally targeted prevention/treatment programs, and recognizing that watching violent television programs may serve as a cue regarding increased susceptibility to nicotine and drug dependence. PMID:18612881

  13. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits

    PubMed Central

    Vieira-Brock, Paula L.; McFadden, Lisa M.; Nielsen, Shannon M.; Smith, Misty D.; Hanson, Glen R.

    2015-01-01

    Background: Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Methods: Adolescent or adult male Sprague-Dawley rats received either nicotine water (10–75 μg/mL) or tap water for several weeks. Methamphetamine (4×7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Results: Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Conclusions: Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which

  14. Difference between the prevalence of symptoms of depression and anxiety in non-diabetic smokers and in patients with type 2 diabetes with and without nicotine dependence

    PubMed Central

    2012-01-01

    Background Individuals with diabetes who are smokers have higher risks of cardiovascular disease, premature death, and microvascular complications. The present study aims to determine the prevalence of symptoms of depression and anxiety in smokers with type 2 diabetes mellitus (T2D) and to evaluate if the prevalence of symptoms of depression and anxiety differ between the three groups studied (patients with T2D who smoke; patients with T2D who do not smoke; smokers without T2D), and finally determine if the degree of nicotine dependence is related to symptoms of anxiety and depression in smokers (with or without T2D). Methods Three study groups were formed: 46 T2D smokers (DS), 46 T2D non-smokers (D), and 46 smokers without diabetes (S), totaling 138 participants. Hospital Anxiety and Depression (HAD) scale and Fagerström Test were applied. Results The prevalence of symptoms of depression and anxiety in smokers with T2D was 30.4% and 50%, respectively. There was no significant difference in the proportion of individuals with symptoms of anxiety (p = 0.072) or depression (p = 0.657) in the DS group compared to group D or S. Among male patients with T2D, the smokers had a higher prevalence of anxiety symptoms (19.6%) than non-smokers (4,3%) (p = 0,025). The prevalence of high nicotine dependence among smokers with and without T2D was 39.1% and 37.1%, respectively (p = 0.999). Fagerström scores showed no significant correlation with the scores obtained on the subscale of anxiety (p = 0,735) or depression (p = 0,364). Conclusions The prevalence of depression and anxiety among smokers with and without diabetes and non-smokers T2D is similar. Among male individuals with T2D, the smokers have more symptoms of anxiety than the non-smokers. There is no difference in the prevalence of nicotine dependence among smokers with and without diabetes. The presence of symptoms of anxiety or depression is similar between patients who are dependent and not

  15. The brain activations for both cue-induced gaming urge and smoking craving among subjects comorbid with Internet gaming addiction and nicotine dependence.

    PubMed

    Ko, Chih-Hung; Liu, Gin-Chung; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Lin, Wei-Chen

    2013-04-01

    Internet gaming addiction (IGA) has been classified as an addictive disorder in the proposed DSM 5 draft. However, whether its underlying addiction mechanism is similar to other substance use disorders has not been confirmed. The present functional magnetic resonance images study is aimed at evaluating the brain correlates of cue-induced gaming urge or smoking craving in subjects with both IGA and nicotine dependence to make a simultaneous comparison of cue induced brain reactivity for gaming and smoking. For this purpose, 16 subjects with both IGA and nicotine dependence (comorbid group) and 16 controls were recruited from the community. All subjects were made to undergo 3-T fMRIs scans while viewing images associated with online games, smoking, and neutral images, which were arranged according to an event-related design. The resultant image data was analyzed with full factorial and conjunction analysis of SPM5. The results demonstrate that anterior cingulate, and parahippocampus activates higher for both cue-induced gaming urge and smoking craving among the comorbid group in comparison to the control group. The conjunction analysis demonstrates that bilateral parahippocampal gyrus activates to a greater degree for both gaming urge and smoking craving among the comorbid group in comparison to the control group. Accordingly, the study demonstrates that both IGA and nicotine dependence share similar mechanisms of cue-induced reactivity over the fronto-limbic network, particularly for the parahippocampus. The results support that the context representation provided by the parahippocampus is a key mechanism for not only cue-induced smoking craving, but also for cue-induced gaming urge.

  16. Tobacco Smoking in Adolescent Psychiatric Outpatients

    ERIC Educational Resources Information Center

    Ditchburn, K. Marie; Sellman, J. Douglas

    2013-01-01

    Three main aims of this study were to ascertain the prevalence rate of smoking among adolescent psychiatric outpatients; estimate smokers' degree of nicotine dependence; and investigate the relationship between smoking and common mental health disorders. Face-to-face interviews were conducted on 93 patients ages 13-18 presenting to an adolescent…

  17. Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure-Activity Relationships and Assessment in a Rat Model of Nicotine Dependence

    PubMed Central

    Sidique, Shyama; Dhanya, Raveendra-Panickar; Sheffler, Douglas J.; Nickols, Hilary Highfield; Yang, Li; Dahl, Russell; Mangravita-Novo, Arianna; Smith, Layton H.; D’Souza, Manoranjan S.; Semenova, Svetlana; Conn, P. Jeffrey; Markou, Athina; Cosford, Nicholas D. P.

    2012-01-01

    Compounds that modulate metabotropic glutamate subtype 2 (mGlu2) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu2 receptor positive allosteric modulators (PAMs). The effects of N-substitution (R1) and substitutions on the aryl ring (R2) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu2 receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans. PMID:23009245

  18. Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

    PubMed Central

    Gould, Thomas J.; Leach, Prescott T.

    2013-01-01

    Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: 1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, 2) how nicotine usurps the cellular mechanisms of synaptic plasticity, 3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal

  19. Addiction and “Generation Me:” Narcissistic and Prosocial Behaviors of Adolescents with Substance Dependency Disorder in Comparison to Normative Adolescents

    PubMed Central

    CARTER, REBECCA R.; JOHNSON, SHANNON M.; EXLINE, JULIE J.; POST, STEPHEN G.; PAGANO, MARIA E.

    2012-01-01

    The purpose of this study is to explore narcissistic and prosocial behaviors as reported by adolescents with and without substance dependency disorder (SDD). This study employs a quasi-experimental design using SDD adolescents compared with two normative samples of adolescents. In comparison to normative adolescents, adolescents with SDD were strongly distinguished by overt narcissistic behaviors and less monetary giving. Levels of narcissistic and prosocial behaviors among adolescents with SDD suggest a connection between self-centeredness and addiction. Results also suggest volunteerism as a potential option to counter narcissism in substance dependent adolescents. PMID:22544995

  20. Long-Term Agonist and Antagonist Therapy for Adolescent Opioid Dependence: A Description of Two Cases

    PubMed Central

    Ranjan, Rajeev; Pattanayak, Raman Deep; Dhawan, Anju

    2014-01-01

    Adolescents constitute only a small percentage of treatment seekers in drug dependence treatment settings. Little research evidence is available for pharmacological treatment of adolescent opioid dependence and no prior case report is available from India. We discuss two adolescent patients with opioid (heroin) dependence visiting a tertiary care center who have been stabilized on agonist (sublingual buprenorphine-naloxone) and antagonist (oral naltrexone) respectively for a substantial period of time. A comprehensive management approach, including intensive psychosocial interventions and family involvement, was followed in addition to pharmacotherapies. More research is needed on the efficacy of pharmacological treatment in adolescent opioid users. PMID:25336782

  1. Cue-Reactivity in Cannabis-Dependent Adolescents

    PubMed Central

    Nickerson, Lisa D.; Ravichandran, Caitlin; Lundahl, Leslie H.; Rodolico, John; Dunlap, Steven; Trksak, George H.; Lukas, Scott E.

    2010-01-01

    We measured event-related potentials (ERPs) with a craving manipulation to investigate the neural correlates of drug cue-reactivity in 13 cannabis-dependent (CD) adolescents (ages 14–17). The P300 responses to marijuana (MJ) pictures (MJ-P300) and control pictures (C-P300) were assessed after handling neutral objects and again after handling MJ paraphernalia (MJP). Self-reported drug craving and heart rates also were measured. MJ-P300 were larger than C-P300 (p<0.001) and both the MJ-P300 and craving increased significantly after handling MJP (p=0.002 and p=0.003, respectively), with no association between the magnitude of craving and MJ-P300. Heart rates were not affected by handling MJP. Our results show that CD adolescents have an attentional bias to MJ stimuli that increases after handling marijuana paraphernalia. Generally, our results are consistent with what has been reported for adult heavy chronic cannabis smokers; although there were some differences that require further investigation. PMID:21142334

  2. Vaccines against nicotine.

    PubMed

    Cerny, Erich H; Cerny, Thomas

    2009-04-01

    Medications against any dependence-inducing drug face a dilemma: if they are efficient, they will induce withdrawal symptoms and the patient is likely to stop taking his medication. Anti drug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting rather with the drug in the blood than with a receptor in the brain, the vaccines are, in addition, free of side effects due to central interaction. For drugs like nicotine interacting with different types of receptors in many organs, this is a further advantage. There are three reasons that anti drug vaccines have first been developed against nicotine. Firstly, in most parts of the world 20 to 50% of the adult population smoke and any smoking cessation treatment will have an important impact on public health and be commercially a very attractive product. The second reason are the smokers themselves, who would like to quit in significant numbers and who have shown good compliance for any form of treatment. Thirdly, the quantities of cocaine or heroine taken by dependant persons are higher than the quantity of nicotine per cigarette, which makes an anti nicotine vaccine the easier vaccine project. Three anti nicotine vaccines are today in an advanced stage of clinical evaluation. We report here how those vaccines work, on the progress of the trials and future developments to expect. Results show that the efficiency of the vaccines is directly related to the antibody levels of the probates, a fact which will help to optimize further the vaccine effect. We expect the vaccines to appear on the market during a time window between 2009 and 2011. PMID:19276649

  3. Association of candidate genes with antisocial drug dependence in adolescents

    PubMed Central

    Corley, Robin P.; Zeiger, Joanna S.; Crowley, Thomas; Ehringer, Marissa A.; Hewitt, John K.; Hopfer, Christian J.; Lessem, Jeffrey; McQueen, Matthew B.; Rhee, Soo Hyun; Smolen, Andrew; Stallings, Michael C.; Young, Susan E.; Krauter, Kenneth

    2008-01-01

    The Colorado Center for Antisocial Drug Dependence (CADD) is using several research designs and strategies in its study of the genetic basis for antisocial drug dependence in adolescents. This study reports Single Nucleotide Polymorphism (SNP) association results from a Targeted Gene Assay (SNP chip) of 231 Caucasian male probands in treatment with antisocial drug dependence and a matched set of community controls. The SNP chip was designed to assay 1500 SNPs distributed across 50 candidate genes that have had associations with substance use disorders and conduct disorder. There was an average gene-wide inter-SNP interval of 3000 base pairs. After eliminating SNPs with poor signals and low minor allele frequencies, 60 nominally significant associations were found among the remaining 1073 SNPs in 18 of 49 candidate genes. Although none of the SNPs achieved genome-wide association significance levels (defined as p < .000001), two genes probed with multiple SNPs (OPRM1 and CHRNA2) emerged as plausible candidates for a role in antisocial drug dependence after gene-based permutation tests. The custom-designed SNP chip served as an effective and flexible platform for rapid interrogation of a large number of plausible candidate genes. PMID:18384978

  4. Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

    PubMed

    Carcoba, Luis M; Orfila, James E; Natividad, Luis A; Torres, Oscar V; Pipkin, Joseph A; Ferree, Patrick L; Castañeda, Eddie; Moss, Donald E; O'Dell, Laura E

    2014-01-01

    Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During

  5. Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

    PubMed

    Carcoba, Luis M; Orfila, James E; Natividad, Luis A; Torres, Oscar V; Pipkin, Joseph A; Ferree, Patrick L; Castañeda, Eddie; Moss, Donald E; O'Dell, Laura E

    2014-01-01

    Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During

  6. Drug Dependence in Adolescents: Changing Trends at a De-Addiction Centre in North India

    ERIC Educational Resources Information Center

    Grover, Sandeep; Basu, Debasish; Mattoo, Surendra Kumar

    2007-01-01

    Introduction: There is scarcity of Indian data on substance dependence in children and adolescents. Methods: Case records of 85 adolescents with the final diagnosis of substance dependence were analyzed (out of 115 registrations during 1978-2003). Results: Time trends showed an increase in individuals with good social support and higher family…

  7. Nicotine and the Developing Human

    PubMed Central

    England, Lucinda J.; Bunnell, Rebecca E.; Pechacek, Terry F.; Tong, Van T.; McAfee, Tim A.

    2015-01-01

    The elimination of cigarettes and other combusted tobacco products in the U.S. would prevent tens of millions of tobacco-related deaths. It has been suggested that the introduction of less harmful nicotine delivery devices, such as electronic cigarettes or other electronic nicotine delivery systems, will accelerate progress toward ending combustible cigarette use. However, careful consideration of the potential adverse health effects from nicotine itself is often absent from public health debates. Human and animal data support that nicotine exposure during periods of developmental vulnerability (fetal through adolescent stages) has multiple adverse health consequences, including impaired fetal brain and lung development, and altered development of cerebral cortex and hippocampus in adolescents. Measures to protect the health of pregnant women and children are needed and could include (1) strong prohibitions on marketing that increase youth uptake; (2) youth access laws similar to those in effect for other tobacco products; (3) appropriate health warnings for vulnerable populations; (4) packaging to prevent accidental poisonings; (5) protection of non-users from exposure to secondhand electronic cigarette aerosol; (6) pricing that helps minimize youth initiation and use; (7) regulations to reduce product addiction potential and appeal for youth; and (8) the age of legal sale. PMID:25794473

  8. Item Response Theory Analysis of DSM-IV Cannabis Abuse and Dependence Criteria in Adolescents

    ERIC Educational Resources Information Center

    Hartman, Christie A.; Gelhorn, Heather; Crowley, Thomas J.; Sakai, Joseph T.; Stallings, Michael; Young, Susan E.; Rhee, Soo Hyun; Corley, Robin; Hewitt, John K.; Hopfer, Christian J.

    2008-01-01

    A study to examine the DSM-IV criteria for cannabis abuse and dependence among adolescents is conducted. Results conclude that abuse and dependence criteria were not found to affect the different levels of severity in cannabis use.

  9. Formaldehyde production promoted by rat nasal cytochrome P-450-dependent monooxygenases with nasal decongestants, essences, solvents, air pollutants, nicotine, and cocaine as substrates

    SciTech Connect

    Dahl, A.R.; Hadley, W.M.

    1983-02-01

    To identify compounds which might be metabolized to formaldehyde in the nasal cavity, 32 potential substrates for cytochrome P-450-dependent monooxygenases were screened with rat nasal and, for comparison, liver microsomes. Tested substrates included 6 nasal decongestants, cocaine, nicotine, 9 essences, 3 potential air pollutants, and 12 solvents. Each test substrate, with the possible exception of the air pollutants, contained one or more N-methyl, O-methyl, or S-methyl groups. Eighteen of the tested materials were metabolized to produce formaldehyde by nasal microsomes. Five substrates, namely, the solvents HMPA and dimethylaniline, cocaine, and the essences dimethyl anthranilate and p-methoxyacetophenone, were metabolized to produce formaldehyde at rates exceeding 1000 pmol/mg microsomal protein/min by nasal microsomes. Eight substrates, including four nasal decongestants, nicotine, and an extract of diesel exhaust particles, were metabolized to produce formaldehyde at rates of 200 to 1000 pmol/mg microsomal protein/min. Five other substrates were metabolized to formaldehyde at detectable rates. The results indicate that a variety of materials which often come in contact with the nasal mucosa can be metabolized to formaldehyde by nasal enzymes. The released formaldehyde may influence the irritancy of inhaled compounds and has been suggested to play a role in the tumorigenicity of some compounds.

  10. Enhanced attenuation of nicotine discrimination in rats by combining nicotine-specific antibodies with a nicotinic receptor antagonist.

    PubMed

    LeSage, Mark G; Shelley, David; Pravetoni, Marco; Pentel, Paul R

    2012-07-01

    Tobacco addiction requires activation by nicotine of a variety of central nicotinic acetylcholine receptors (nAChRs). In animals, both nAChR antagonists and immunization against nicotine can reduce nAChR activation by nicotine and block a variety of addiction-relevant behaviors. However, clinical use of nAChR antagonists for smoking cessation is limited by dose-related side effects, and immunization does not reliably produce sufficient antibody levels in smokers to enhance smoking cessation rates. Combining these approaches may be one way of addressing the limitations of each while enhancing overall efficacy. This study examined the individual and combined effects of passive immunization with the monoclonal nicotine-specific antibody Nic311 and the nicotinic receptor antagonist mecamylamine (MEC) on nicotine's discriminative stimulus effects. Rats were trained to discriminate 0.4 mg/kg of nicotine from saline using a two-lever operant discrimination procedure. Antagonism of nicotine discrimination by Nic311 (160 mg/kg i.v.) and ascending doses of MEC (0.03, 0.1, 0.3, and 1.0 mg/kg s.c.) was assessed across four consecutive daily 2-min extinction test sessions using a 2×2 design. Nic311 alone produced a 24-48% reduction in % nicotine-lever responding (%NLR) across all four test sessions. MEC produced a dose-dependent decrease in %NLR, with no effect at the two lowest doses and 80-93% attenuation at the two highest doses. Nic311 combined with MEC significantly suppressed %NLR at every MEC dose (85-92% reduction across all four test sessions). Very low doses of MEC that were ineffective alone completely blocked nicotine discrimination when combined with Nic311. These data demonstrate that nicotine-specific antibodies and MEC can work synergistically to suppress the subjective effects of nicotine and suggest that low doses of MEC may significantly enhance the efficacy of immunotherapy.

  11. Nicotinic receptors and attention.

    PubMed

    Hahn, Britta

    2015-01-01

    Facilitation of different attentional functions by nicotinic acetylcholine receptor (nAChR) agonists may be of therapeutic potential in disease conditions such as Alzheimer's disease or schizophrenia. For this reason, the neuronal mechanisms underlying these effects have been the focus of research in humans and in preclinical models. Attention-enhancing effects of the nonselective nAChR agonist nicotine can be observed in human nonsmokers and in laboratory animals, suggesting that benefits go beyond a reversal of withdrawal deficits in smokers. The ultimate aim is to develop compounds acting with greater selectivity than nicotine at a subset of nAChRs, with an effects profile narrowly matching the targeted cognitive deficits and minimizing unwanted effects. To date, compounds tested clinically target the nAChR subtypes most abundant in the brain. To help pinpoint more selectively expressed subtypes critical for attention, studies have aimed at identifying the secondary neurotransmitter systems whose stimulation mediates the attention-enhancing properties of nicotine. Evidence indicates that noradrenaline and glutamate, but not dopamine release, are critical mediators. Thus, attention-enhancing nAChR agents could spare the system central to nicotine dependence. Neuroimaging studies suggest that nAChR agonists act on a variety of brain systems by enhancing activation, reducing activation, and enhancing deactivation by attention tasks. This supports the notion that effects on different attentional functions may be mediated by distinct central mechanisms, consistent with the fact that nAChRs interact with a multitude of brain sites and neurotransmitter systems. The challenge will be to achieve the optimal tone at the right subset of nAChR subtypes to modulate specific attentional functions, employing not just direct agonist properties, but also positive allosteric modulation and low-dose antagonism.

  12. The Role of Nicotine in Schizophrenia.

    PubMed

    Featherstone, Robert E; Siegel, Steven J

    2015-01-01

    Schizophrenia is associated with by severe disruptions in thought, cognition, emotion, and behavior. Patients show a marked increase in rates of smoking and nicotine dependence relative to nonaffected individuals, a finding commonly ascribed to the potential ameliorative effects of nicotine on symptom severity and cognitive impairment. Indeed, many studies have demonstrated improvement in patients following the administration of nicotine. Such findings have led to an increased emphasis on the development of therapeutic agents to target the nicotinic system as well as increasing the impetus to understand the genetic basis for nicotinic dysfunction in schizophrenia. The goal of this review article is to provide a critical summary of evidence for the role of the nicotinic system in schizophrenia. The first part will review the role of nicotine in normalization of primary dysfunctions and endophenotypical changes found in schizophrenia. The second part will provide a summary of genetic evidence linking polymorphisms in nicotinic receptor genes to smoking and schizophrenia. The third part will summarize attempts to treat schizophrenia using agents specifically targeting nicotinic and nicotinic receptor subtypes. Although currently available antipsychotic treatments are generally able to manage some aspects of schizophrenia (e.g., positive symptoms) they fail to address several other critically effected aspects of the disease. As such, the search for novel mechanisms to treat this disease is necessary. PMID:26472525

  13. Psychophysiological interactions between caffeine and nicotine.

    PubMed

    Rose, J E; Behm, F M

    1991-02-01

    The interactive effects of caffeine and nicotine were studied in twelve subjects. Mood and physiologic responses to the pharmacologic components nicotine and caffeine were measured, while controlling for the sensory/behavioral aspects of smoking and coffee drinking. Two experimental sessions presented a caffeine x nicotine design, with caffeinated or decaffeinated coffee followed at thirty-minute intervals by controlled inhalations of nicotine and nonnicotine smoke. Results showed that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. These findings extend previous work showing interactive effects of caffeine and self-titrated doses of cigarette smoke in affecting subjective arousal. The effects of nicotine on subjective arousal may, therefore, depend not only on nicotine dose, but also on the presence of caffeine. Heart rate was increased by nicotine and both systolic and diastolic blood pressures were elevated by caffeine. Caffeine also potentiated the increase in diastolic blood pressure resulting from smoke inhalations, but this occurred irrespective of nicotine dose. PMID:2057503

  14. The Role of Nicotine in Schizophrenia.

    PubMed

    Featherstone, Robert E; Siegel, Steven J

    2015-01-01

    Schizophrenia is associated with by severe disruptions in thought, cognition, emotion, and behavior. Patients show a marked increase in rates of smoking and nicotine dependence relative to nonaffected individuals, a finding commonly ascribed to the potential ameliorative effects of nicotine on symptom severity and cognitive impairment. Indeed, many studies have demonstrated improvement in patients following the administration of nicotine. Such findings have led to an increased emphasis on the development of therapeutic agents to target the nicotinic system as well as increasing the impetus to understand the genetic basis for nicotinic dysfunction in schizophrenia. The goal of this review article is to provide a critical summary of evidence for the role of the nicotinic system in schizophrenia. The first part will review the role of nicotine in normalization of primary dysfunctions and endophenotypical changes found in schizophrenia. The second part will provide a summary of genetic evidence linking polymorphisms in nicotinic receptor genes to smoking and schizophrenia. The third part will summarize attempts to treat schizophrenia using agents specifically targeting nicotinic and nicotinic receptor subtypes. Although currently available antipsychotic treatments are generally able to manage some aspects of schizophrenia (e.g., positive symptoms) they fail to address several other critically effected aspects of the disease. As such, the search for novel mechanisms to treat this disease is necessary.

  15. Subjective effects of transdermal nicotine among nonsmokers.

    PubMed

    Ashare, Rebecca L; Baschnagel, Joseph S; Hawk, Larry W

    2010-04-01

    The subjective experience of nicotine, which may be influenced by personality traits as well as environmental factors, may be important for understanding the factors associated with the initiation and maintenance of nicotine dependence. The present study examined the effects of 7 mg transdermal nicotine among a relatively large sample (n = 91; 44 women) of college-aged nonsmokers. Using a placebo controlled, double-blind, within-subjects design, nicotine's effects were examined at rest and again after participants completed a sustained attention task. Sex and personality factors (Behavioral Inhibition and Behavioral Approach; BIS/BAS Scales; Carver & White, 1994) were examined as potential moderators. Overall, the effects of nicotine were generally modest and unpleasant. In the context of the cognitive task, nicotine increased nausea and negative affect but reduced fatigue, relative to placebo. In contrast, effects of nicotine during the initial 4 hr of patch administration, in which participants were in their natural environments, were moderated by individual differences in behavioral approach. Neither behavioral inhibition nor gender reliably moderated any subjective effects of nicotine. The present work suggests transdermal nicotine exerts only modest, mostly negative effects among nonsmokers. Future work should examine both contextual and personality moderators in large samples of participants who are exposed to nicotine through multiple routes of administration. PMID:20384428

  16. Are you in or out? Recruitment of adolescent smokers into a behavioral smoking cessation intervention

    PubMed Central

    Thrul, Johannes; Stemmler, Mark; Goecke, Michaela; Bühler, Anneke

    2015-01-01

    Even though many adolescent smokers want to quit, it is difficult to recruit them into smoking cessation interventions. Little is known about which adolescent smokers are currently reached by these measures. In this study we compare participants of a group-based, cognitive behavioral smoking cessation intervention with adolescent smokers who decided against participating. Within a non-randomized controlled trial, data of 1053 smokers (age 11–19) from 42 German secondary schools were analyzed. Of these smokers, 272 were recruited into 47 courses of the intervention. An in-class information session, individually addressing potential participants, and incentives were used as means of recruitment. Personal predictors of participation were analyzed using regression analyses and multivariate path analyses to test for mediation. In the path analysis model, nicotine dependence, quit motivation, and a previous quit attempt were directly positively related to participation. Heavier smoking behavior was indirectly positively associated with participation through nicotine dependence and negatively through quit motivation, yielding an overall positive indirect effect. The positive effect of a previous quit attempt on participation was partially mediated through nicotine dependence and quit motivation. The proportion of smoking friends were indirectly positively related to participation, mediated through nicotine dependence. Since adolescents with heavier smoking behavior and stronger nicotine dependence are less likely to undertake a successful unassisted quit attempt, the reach of these young smokers with professional cessation interventions is desirable. Further measures to improve the recruitment of those currently not motivated to quit have to be examined in future studies. PMID:25678303

  17. The α3β4* nicotinic acetylcholine receptor subtype mediates nicotine reward and physical nicotine withdrawal signs independently of the α5 subunit in the mouse

    PubMed Central

    Jackson, Kia J.; Sanjakdar, Sarah S.; Muldoon, Pretal P.; McIntosh, J. Michael; Damaj, M. Imad

    2013-01-01

    The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 nAChR subunits in nicotine dependence and withdrawal; however studies focusing on the behavioral role of the α3β4* nAChR receptor subtype in nicotine dependence are lacking. Because of the apparent role of the α3β4* nAChR subtype in nicotine dependence, the goal of the current study was to better evaluate the involvement of this subtype in nicotine mediated behavioral responses. Using the selective α3β4* nAChR antagonist, α-conotoxin AuIB, we assessed the role of α3β4* nAChRs in acute nicotine, nicotine reward, and physical and affective nicotine withdrawal. Because α5 has also been implicated in nicotine dependence behaviors in mice and can form functional receptors with α3β4*, we also evaluated the role of the α3β4α5* nAChR subtype in nicotine reward and somatic nicotine withdrawal signs by blocking the α3β4* nAChR subtype in α5 nAChR knockout mice with AuIB. AuIB had no significant effect on acute nicotine behaviors, but dose-dependently attenuated nicotine reward and physical withdrawal signs, with no significant effect in affective withdrawal measures. Interestingly, AuIB also attenuated nicotine reward and somatic signs in α5 nAChR knockout mice. This study shows that α3β4* nAChRs mediate nicotine reward and physical nicotine withdrawal, but not acute nicotine behaviors or affective nicotine withdrawal signs in mice. The α5 subunit is not required in the receptor assembly to mediate these effects. Our findings suggest an important role for the α3β4* nAChR subtype in nicotine reward and physical aspects of the nicotine withdrawal syndrome. PMID:23416040

  18. The α3β4* nicotinic acetylcholine receptor subtype mediates nicotine reward and physical nicotine withdrawal signs independently of the α5 subunit in the mouse.

    PubMed

    Jackson, Kia J; Sanjakdar, Sarah S; Muldoon, Pretal P; McIntosh, J Michael; Damaj, M Imad

    2013-07-01

    The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 nAChR subunits in nicotine dependence and withdrawal; however studies focusing on the behavioral role of the α3β4* nAChR receptor subtype in nicotine dependence are lacking. Because of the apparent role of the α3β4* nAChR subtype in nicotine dependence, the goal of the current study was to better evaluate the involvement of this subtype in nicotine mediated behavioral responses. Using the selective α3β4* nAChR antagonist, α-conotoxin AuIB, we assessed the role of α3β4* nAChRs in acute nicotine, nicotine reward, and physical and affective nicotine withdrawal. Because α5 has also been implicated in nicotine dependence behaviors in mice and can form functional receptors with α3β4*, we also evaluated the role of the α3β4α5* nAChR subtype in nicotine reward and somatic nicotine withdrawal signs by blocking the α3β4* nAChR subtype in α5 nAChR knockout mice with AuIB. AuIB had no significant effect on acute nicotine behaviors, but dose-dependently attenuated nicotine reward and physical withdrawal signs, with no significant effect in affective withdrawal measures. Interestingly, AuIB also attenuated nicotine reward and somatic signs in α5 nAChR knockout mice. This study shows that α3β4* nAChRs mediate nicotine reward and physical nicotine withdrawal, but not acute nicotine behaviors or affective nicotine withdrawal signs in mice. The α5 subunit is not required in the receptor assembly to mediate these effects. Our findings suggest an important role for the α3β4* nAChR subtype in nicotine reward and physical aspects of the nicotine withdrawal syndrome.

  19. Public Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke.

    PubMed

    Farber, Harold J; Nelson, Kevin E; Groner, Judith A; Walley, Susan C

    2015-11-01

    Tobacco use and tobacco smoke exposure are among the most important health threats to children, adolescents, and adults. There is no safe level of tobacco smoke exposure. The developing brains of children and adolescents are particularly vulnerable to the development of tobacco and nicotine dependence. Tobacco is unique among consumer products in that it causes disease and death when used exactly as intended. Tobacco continues to be heavily promoted to children and young adults. Flavored and alternative tobacco products, including little cigars, chewing tobacco, and electronic nicotine delivery systems are gaining popularity among youth. This statement describes important evidence-based public policy actions that, when implemented, will reduce tobacco product use and tobacco smoke exposure among youth and, by doing so, improve the health of children and young adults. PMID:26504133

  20. Psychiatric Syndromes in Adolescents with Marijuana Abuse and Dependency in Outpatient Treatment

    ERIC Educational Resources Information Center

    Diamond, Guy; Panichelli-Mindel, Susan M.; Shera, David; Dennis, Mike; Tims, Frank; Ungemack, Jane

    2006-01-01

    Objective: The purpose of the current study to assist in understanding the prevalence and clinical correlates of psychiatric distress in adolescents seeking outpatient services for marijuana abuse or dependency. Methods: In a multi-site randomized clinical trial, 600 adolescents and their parents were assessed at intake using the Global Appraisals…

  1. Innovative Adolescent Chemical Dependency Treatment and Its Outcome: A Model Based on Outward Bound Programming.

    ERIC Educational Resources Information Center

    McPeake, John D.; And Others

    1991-01-01

    Describes adolescent chemical dependency treatment model developed at Beech Hill Hospital (New Hampshire) which integrated Twelve Step-oriented alcohol and drug rehabilitation program with experiential education school, Hurricane Island Outward Bound School. Describes Beech Hill Hurricane Island Outward Bound School Adolescent Chemical Dependency…

  2. Prevalence of Mobile Phone Dependence in Secondary School Adolescents

    PubMed Central

    Nikhita, Chimatapu Sri; Jadhav, Pradeep R

    2015-01-01

    Introduction Mobile phones have become an essential part of modern human life. They have many attributes which makes them very attractive to both young and old. There has been an increasing trend of use of mobile phones among students. Data has now started emerging with respect to the negative physical and psychological consequences of excessive use of mobile phones. New research has shown excessive use of mobile phones leading to development of symptoms suggestive of dependence syndrome. Aim To study the prevalence of Mobile Phone Dependence (MPD) in secondary school adolescents. Setting and Design Cross-sectional, observational study conducted in secondary section of English-medium schools at Navi Mumbai (India). Materials and Methods Four hundred and fifteen students studying in 8th, 9th and 10th standards of schools at Navi Mumbai (India) having personal mobile phone were randomly included in the study. Participant information like age, gender, family type, phone type, duration of use per day and years of mobile phone usage was recorded. They were administered an MPD questionnaire based upon the dependence syndrome criteria as per ICD-10. According to their responses, participants who fulfilled three or more of the diagnostic criteria were rated as having MPD. Results Mobile Phone Dependence was found in 31.33% of sample students. It was significantly associated with gender (p=0.003, OR=1.91, CI: 1.23-2.99), family type (p=0.0012), type of mobile phone used (p<0.001, OR=2.6, CI: 1.63-4.35), average time per day spent using mobile phone (p<0.001) and years of mobile phone usage (p =0.004, OR=2.4, CI: 1.31-4.55). Conclusion Mobile Phone Dependence has been found to be an emerging public health problem. There is need to recognize and identify early the growing trends and negative consequences of inappropriate mobile phone use in young users so as to generate awareness, and plan educational and treatment interventions, if need be, so as to prevent a major public

  3. Suicidal ideation and attempts among chemically dependent adolescents.

    PubMed Central

    Deykin, E Y; Buka, S L

    1994-01-01

    OBJECTIVES. Suicidal ideation and attempts were examined in a population of chemically dependent adolescents, a group at high risk of self-destructive behavior. METHODS. The prevalence and correlates of suicidality and of major depressive disorder were assessed by the Diagnostic Interview Schedule and a structured family and social history interview with 300 addicts aged 15 through 19 years. RESULTS. Suicidal ideation was reported by 31% to 75% of the subjects and suicide attempts were reported by 28% to 61%, with females predominating. Thoughts of suicide combined with prolonged thoughts of death in general and a desire to be dead were highly associated with suicide attempts. Exposure to physical or sexual abuse was associated with a significantly increased risk of suicide attempts for males but not for females. CONCLUSIONS. The probability of a suicide attempt increases when thoughts of suicide coincide with morbid ideation of extended duration, suggesting that risk assessment should be based on duration as well as presence of morbid thoughts. Substance abuse treatment requires an assessment of suicidal potential and counseling for those whose potential is high, with special attention to males exposed to abuse. PMID:8154569

  4. Prescription Pain Reliever Abuse and Dependence among Adolescents: A Nationally Representative Study

    ERIC Educational Resources Information Center

    Wu, Li-Tzy; Ringwalt, Christopher L.; Mannelli, Paolo; Patkar, Ashwin A.

    2008-01-01

    The study investigates the prevalence, patterns, and correlates of adolescents' abuse, sub-threshold dependence, and dependence on prescription pain relievers (PPRs) in a nationally representative sample. Results show dependence on PPRs can take place without abuse and that sub-threshold dependence could have implications for major diagnostic…

  5. New mechanisms and perspectives in nicotine withdrawal

    PubMed Central

    Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

    2014-01-01

    Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

  6. Intracerebellar behavioral interactions between nicotine, cotinine and ethanol in mice

    SciTech Connect

    Dar, M.S.; Li, C. )

    1992-02-26

    Using ethanol-induced motor incoordination as the test response as evaluated by rotorod, possible behavioral interactions between ethanol and (-)-nicotine in the cerebellum, one of the key motor area, were investigated. (-)-Nicotine, 5, 1.25, 0.625 ng/100nL intracerebellarly significantly attenuated motor incoordination due to ethanol in a dose-dependent manner. Similarly, (-)-cotinine, a major metabolite of nicotine, 5, 2.5, and 1.25 ng/100nL, significantly but less marked compared to (-)-nicotine attenuated ethanol-induced motor incoordination. The highest, 5 ng/100nL, dose of (-)-nicotine or (-)-cotinine followed by saline instead of ethanol did not alter normal motor coordination. The attenuation of ethanol-induced motor incoordination by (-)-nicotine and (-)- cotinine was blocked by intracerebellar hexamethonium 1 ug/100nL, a purported nicotinic cholinergic antagonist. The data obtained strongly suggest participation of cerebellar nicotinic cholinergic receptor in the ethanol-induced motor incoordination.

  7. Nicotinic receptor-dependent and -independent effects of galantamine, an acetylcholinesterase inhibitor, on the non-neuronal acetylcholine system in C2C12 cells.

    PubMed

    Oikawa, Shino; Mano, Asuka; Iketani, Mitsue; Kakinuma, Yoshihiko

    2015-11-01

    We previously reported that satellite cells possess the ability to produce angiogenic factors, including fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF) in vivo. However, whether C2C12 cells possess a non-neuronal cholinergic system (NNCS) or non-neuronal ACh (NNA) remains to be studied; therefore, we investigated the system using C2C12 cells and its regulatory mechanisms. C2C12 cells synthesized ACh, the level of which was comparable with that of cardiomyocytes, and the synthesis was augmented by the acetylcholinesterase inhibitor galantamine. The ChAT promoter activity was upregulated by nicotine or galantamine, partly through nicotinic receptors for both agents as well as through a non-nicotinic receptor pathway for galantamine. Further, VEGF secretion by C2C12 cells was also increased by nicotine or galantamine through nicotinic receptors as well as partly through non-nicotinic pathways in the case of galantamine. These results suggest that C2C12 cells are equipped with NNCS or NNA, which is positively regulated through nicotinic or non-nicotinic pathways, particularly in the case of galantamine. These results provide a novel concept that myogenic cells expressing NNA can be a therapeutic target for regulating angiogenic factor synthesis. PMID:25979761

  8. A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration

    PubMed Central

    Cippitelli, Andrea; Schoch, Jennifer; Debevec, Ginamarie; Brunori, Gloria; Zaveri, Nurulain T.; Toll, Lawrence

    2016-01-01

    Alcohol and nicotine are often co-abused. Although the N/OFQ-NOP receptor system is considered a potential target for development of drug abuse pharmacotherapies, especially for alcoholism, little is known about the role of this system in nicotine dependence. Furthermore, the effect of prior history of nicotine dependence on subsequent nicotine and alcohol taking is understudied. Using an operant co-administration paradigm, in which rats concurrently self-administer nicotine and alcohol, we found that nicotine dependent rats increased nicotine self-administration over time as compared to non-dependent animals, while patterns of alcohol lever pressing did not change between groups. Pretreatment with the potent NOP receptor agonist AT-202 (0.3–3 mg/kg) increased nicotine lever pressing of both dependent and non-dependent groups, whereas the selective antagonist SB612111 (1–10 mg/kg) elicited a clear reduction of nicotine responses, in both dependent and non-dependent rats. In parallel, AT-202 only produced minor changes on alcohol responses and SB612111 reduced alcohol taking at a dose that also reduced locomotor behavior. Results indicate that a history of nicotine dependence affects subsequent nicotine- but not alcohol-maintained responding, and that NOP receptor antagonism, rather than agonism, blocks nicotine self-administration, which strongly suggests a critical role for the endogenous N/OFQ in the modulation of nicotine reinforcement processes. PMID:27199205

  9. Neuroimaging, Genetics and the Treatment of Nicotine Addiction

    PubMed Central

    Ray, Riju; Loughead, James; Wang, Ze; Detre, John; Yang, Edward; Gur, Ruben; Lerman, Caryn

    2008-01-01

    Advances in neuroimaging and genomics provide an unprecedented opportunity to accelerate medication development for nicotine dependence and other addictions. Neuroimaging studies have begun to elucidate the functional neuroanatomy and neurochemistry underlying effects of nicotine and nicotine abstinence. In parallel, genetic studies, including both candidate gene and genome-wide association approaches, are identifying key neurobiological targets and pathways important in addiction to nicotine. To date, only a few neuroimaging studies have explored effects of nicotine or abstinence on brain activity as a function of genotype. Most analyses of genotype are retrospective, resulting in small sample sizes for testing effects of the minor alleles for candidate genes. The purpose of this review is to provide an outline of the work in neuroimaging, genetics, and nicotine dependence, and to explore the potential for increased integration of these approaches to improve nicotine dependence treatment. PMID:18599130

  10. Role of α5 Nicotinic Acetylcholine Receptors in Pharmacological and Behavioral Effects of Nicotine in Mice

    PubMed Central

    Marks, M. J.; Vann, R. E.; Chen, X.; Gamage, T. F.; Warner, J. A.; Damaj, M. I.

    2010-01-01

    Incorporation of the α5 nicotinic acetylcholine receptor (nAChR) subunit can greatly influence nAChR function without altering receptor number. Although few animal studies have assessed the role of the α5 nAChR in nicotine-mediated behaviors, recent evidence suggests an association between polymorphisms in the α5 nAChR gene and nicotine dependence phenotypes in humans. Thus, additional studies are imperative to elucidate the role and function of the α5 nAChR subunit in nicotine dependence. Using α5(−/−) mice, the current study aimed to examine the role of α5 nAChRs in the initial pharmacological effects of nicotine, nicotine reward using the conditioned place preference model, and the discriminative effects of nicotine using a two-lever drug discrimination model. 86Rb+ efflux and 125I-epibatidine binding assays were conducted to examine the effect of α5 nAChR subunit deletion on expression and activity of functional nAChRs. Results show that α5(−/−) mice are less sensitive to the initial effects of nicotine in antinociception, locomotor activity, and hypothermia measures and that the α5 nAChR is involved in nicotine reward. Alternatively, α5(−/−) mice did not differ from wild-type littermates in sensitivity to the discriminative stimulus effects of nicotine. Furthermore, deletion of the α5 nAChR subunit resulted in a statistically significant decrease in function in the thalamus and hindbrain, but the decreases noted in spinal cord were not statistically significant. Receptor number was unaltered in all areas tested. Taken together, results of the study suggest that α5 nAChRs are involved in nicotine-mediated behaviors relevant to development of nicotine dependence. PMID:20400469

  11. Toxicological Analysis of Low-Nicotine and Nicotine-Free Cigarettes

    PubMed Central

    Chen, Jinguo; Higby, Richard; Tian, Defa; Tan, Duanjun; Johnson, Michael D.; Xiao, Yingxian; Kellar, Kenneth J; Feng, Shibao; Shields, Peter G.

    2008-01-01

    Low-nicotine and nicotine-free cigarettes are commercially available under the brand-name Quest®. Some consumers may believe that these are safer cigarettes, and they may smoke more cigarettes or inhale more smoke to compensate for low nicotine yields. Thus, we have studied the toxicological effects of these two cigarettes and compared them with the Kentucky reference cigarette 2R4F. Also, the availability of nicotine-free cigarettes allows for the assessing the role of nicotine in cigarette smoke. In addition to nicotine, some tobacco-specific nitrosamines, aldehydes, and volatile organic compounds were also reduced in the Quest® cigarettes compared to the 2R4F. However, aromatic amines were higher in the nicotine-free compared with low nicotine cigarettes. The Ames test revealed that cigarette smoke condensates from the nicotinefree (CSC-F), low nicotine (CSC-L) and 2R4F (CSC-R) cigarettes had a similar mutagenic potency. Exposure to any CSC caused a similar dose-dependent LDH leakage from normal human bronchial epithelial cells. However, CSC-F had more inhibitory effects on the cell growth than CSC-L and CSC-R. Adding nicotine to the CSC-F attenuated this inhibition. Both Quest® CSCs decreased gap junction intercellular communication and caused cell cycle arrest. CSC exposure increased cytoplasmic nucleosomes, sub-G1/G0 population and apoptotic comet tails. Proapoptotic protein Bax increased independent of p53 induction after exposure to CSC-F. In conclusion, these studies are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells. Nicotine, as it exists in CSC, attenuates cytotoxicity possibly in part through inhibition of apoptotic pathways. PMID:18599178

  12. Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells.

    PubMed

    Fu, Xiao Wen; Lindstrom, Jon; Spindel, Eliot R

    2009-07-01

    Prenatal nicotine exposure impairs normal lung development and leads to diminished pulmonary function after birth. Previous work from our laboratory has demonstrated that nicotine alters lung development by affecting a nonneuronal cholinergic autocrine loop that is expressed in lung. Bronchial epithelial cells (BECs) express choline acetyltransferase, the choline high-affinity transporter and nicotinic acetylcholine (ACh) receptor (nAChR) subunits. We now demonstrate through a combination of morphological and electrophysiological techniques that nicotine affects this autocrine loop by up-regulating and activating cholinergic signaling. RT-PCR showed the expression of alpha 3, alpha 4, alpha 7, alpha 9, alpha 10, beta2, and beta 4 nAChR mRNAs in rhesus monkey lung and cultured BECs. The expression of alpha 7, alpha 4, and beta2 nAChR was confirmed by immunofluorescence in the cultured BECs and lung. The electrophysiological characteristics of nAChR in BECs were determined using whole-cell patch-clamp on cultured BECs. Both ACh and nicotine evoked an inward current, with a rapid desensitizing current. Nicotine induced inward currents in a concentration-dependent manner, with an EC(50) of 26.7 microM. Nicotine-induced currents were reversibly blocked by the nicotinic antagonists, mecamylamine, dihydro-beta-erythroidine, and methyllcaconitine. Incubation of BECs with 1 microM nicotine for 48 hours enhanced nicotine-induced currents by roughly 26%. The protein tyrosine phosphorylation inhibitor, genistein, increased nicotine-induced currents by 58% and enhanced methyllcaconitine-sensitive currents (alpha 7 nAChR activities) 2.3-fold, whereas the protein tyrosine phosphatase inhibitor, pervanadate, decreased the effects of nicotine. These results demonstrate that chronic nicotine exposure up-regulates nAChR activity in developing lung, and that nAChR activity can be further modified by tyrosine phosphorylation.

  13. Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review.

    PubMed

    Le Houezec, J

    2003-09-01

    Smoking is a complex behaviour involving both pharmacological and psychological components. Nicotine is the main alkaloid found in tobacco, and is responsible for its addictive potential. Nicotine-positive effects on mood and cognition are strong reinforcements for smokers that contribute to their addiction, and cigarette smoking is particularly addictive because inhaled nicotine is absorbed through the pulmonary venous rather than the systemic venous system, and thus reaches the brain in 10-20 seconds. As the likelihood that a substance will be abused depends on the time between administration and central reinforcement, tobacco smoking can easily become addictive. Nicotine replacement therapy (NRT) is available in different forms (gum, transdermal patch, nasal spray, inhaler, sublingual tablet and lozenge), and has been shown to relieve withdrawal symptoms and to double abstinence rates compared to placebo. Most NRT forms deliver nicotine more slowly than smoking, and the increase in nicotine blood levels is more gradual. Compared to tobacco smoking or even tobacco chewing, few positive (reinforcing) effects are obtained from NRT use. Nasal spray provides faster withdrawal relief than other NRT, but compared to smoking absorption is slower and nicotine blood levels obtained are lower than with smoking. These differences in pharmacokinetic profiles compared with smoking may explain that some smokers still have difficulties quitting smoking even when using NRT (apart from psychological and/or social factors). Combination therapy (e.g., patch+gum, patch+inhaler), higher dosage, temporary abstinence or smoking reduction (using NRT to reduce smoke intake) may be needed to help more smokers to quit. PMID:12971663

  14. Do Personality Characteristics and Risk Taking Mediate the Relationship Between Paternal Substance Dependence and Adolescent Substance Use?

    PubMed Central

    Ohannessian, Christine McCauley; Hesselbrock, Victor M.

    2007-01-01

    This longitudinal study examined whether adolescent personality characteristics and risk taking mediate the relationship between paternal substance dependence and adolescent substance use. At Time 1, the sample included 249 15–19 year-old adolescents and their fathers. These individuals also were assessed five years later (Time 2). Results indicated that paternal substance dependence directly and indirectly (via personality and risk taking) predicted adolescent substance use. Paternal substance dependence had significant direct effects on age when the adolescent first used marijuana and significant indirect effects on age when regular drinking began, age when first used marijuana, and frequency of drinking to get “high” or “drunk.” All of the indirect personality effects were via adolescent disinhibition. In addition, adolescent risk taking further mediated personality and adolescent substance use. Results from this study are discussed in relation to an epigenetic perspective of human development. PMID:17241748

  15. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats.

    PubMed

    Poliacek, I; Rose, M J; Pitts, T E; Mortensen, A; Corrie, L W; Davenport, P W; Bolser, D C

    2015-02-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (-)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (-)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (-)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (-)nicotine for inhibition of cough. Microinjections of (-)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism.

  16. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats

    PubMed Central

    Rose, M. J.; Pitts, T. E.; Mortensen, A.; Corrie, L. W.; Davenport, P. W.; Bolser, D. C.

    2014-01-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (−)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (−)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (−)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (−)nicotine for inhibition of cough. Microinjections of (−)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism. PMID:25477349

  17. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats.

    PubMed

    Poliacek, I; Rose, M J; Pitts, T E; Mortensen, A; Corrie, L W; Davenport, P W; Bolser, D C

    2015-02-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (-)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (-)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (-)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (-)nicotine for inhibition of cough. Microinjections of (-)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism. PMID:25477349

  18. Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

    PubMed

    Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B

    2016-01-01

    Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences. PMID:26872268

  19. Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner

    PubMed Central

    Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B.

    2016-01-01

    Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood—under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45–51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences. PMID:26872268

  20. Nicotine-motivated behavior in Caenorhabditis elegans requires the nicotinic acetylcholine receptor subunits acr-5 and acr-15.

    PubMed

    Sellings, Laurie; Pereira, Schreiber; Qian, Cheng; Dixon-McDougall, Thomas; Nowak, Christina; Zhao, Bin; Tyndale, Rachel F; van der Kooy, Derek

    2013-03-01

    Signaling at nicotinic acetylcholine receptors in Caenorhabditis elegans controls many behaviors, including egg-laying and locomotor activity. Here, we show that C. elegans approaches a point source of nicotine in a time-, concentration- and age-dependent manner. Additionally, nicotine paired with butanone under starvation conditions prevented the reduced approach to butanone that is observed when butanone is paired with starvation alone and pairing with nicotine generates a preference for the tastes of either sodium or chloride over baseline. These results suggest nicotine acts as a rewarding substance in C. elegans. Furthermore, the nicotinic receptor antagonist mecamylamine, the smoking cessation pharmacotherapy varenicline, mutation of the dop-1 and dop-2 dopamine receptors, and mutations of either acr-5 or acr-15, two nicotinic receptor subunit genes with sequence homology to the mammalian α7 subunit, all reduced the nicotine approach behavior. These two mutants also were defective at associating the presence of nicotine with butanone under starvation conditions and acr-5 mutation could obviate the effect of pairing nicotine with salts. Furthermore, the approach deficit in acr-15 mutants was rescued by selective re-expression in a subset of neurons, but not in muscle. Caenorhabditis elegans may therefore serve as a useful model organism for nicotine-motivated behaviors that could aid in the identification of novel nicotine motivational molecular pathways and consequently the development of novel cessation aids.

  1. Adolescent brain maturation and smoking: what we know and where we're headed.

    PubMed

    Lydon, David M; Wilson, Stephen J; Child, Amanda; Geier, Charles F

    2014-09-01

    Smoking is a leading cause of mortality and morbidity worldwide. Smoking initiation often occurs during adolescence. This paper reviews and synthesizes adolescent development and nicotine dependence literatures to provide an account of adolescent smoking from onset to compulsive use. We extend neurobiological models of adolescent risk-taking, that focus on the interplay between incentive processing and cognitive control brain systems, through incorporating psychosocial and contextual factors specific to smoking, to suggest that adolescents are more vulnerable than adults to cigarette use generally, but that individual differences exist placing some adolescents at increased risk for smoking. Upon smoking, adolescents are more likely to continue smoking due to the increased positive effects induced by nicotine during this period. Continued use during adolescence, may be best understood as reflecting drug-related changes to neural systems underlying incentive processing and cognitive control, resulting in decision-making that is biased towards continued smoking. Persistent changes following nicotine exposure that may underlie continued dependence are described. We highlight ways that interventions may benefit from a consideration of cognitive-neuroscience findings.

  2. Adolescent Brain Maturation and Smoking: What We Know and Where We’re Headed

    PubMed Central

    Lydon, David M.; Wilson, Stephen J.; Child, Amanda; Geier, Charles F.

    2015-01-01

    Smoking is a leading cause of mortality and morbidity worldwide. Smoking initiation often occurs during adolescence. This paper reviews and synthesizes adolescent development and nicotine dependence literatures to provide an account of adolescent smoking from onset to compulsive use. We extend neurobiological models of adolescent risk-taking, that focus on the interplay between incentive processing and cognitive control brain systems, through incorporating psychosocial and contextual factors specific to smoking, to suggest that adolescents are more vulnerable than adults to cigarette use generally, but that individual differences exist placing some adolescents at increased risk for smoking. Upon smoking, adolescents are more likely to continue smoking due to the increased positive effects induced by nicotine during this period. Continued use during adolescence, may be best understood as reflecting drug-related changes to neural systems underlying incentive processing and cognitive control, resulting in decision-making that is biased towards continued smoking. Persistent changes following nicotine exposure that may underlie continued dependence are described. We highlight ways that interventions may benefit from a consideration of cognitive-neuroscience findings. PMID:25025658

  3. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

    PubMed

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Ellis, Jonathan D; Walters, Elliot T; Stout, Kristen A; McIntosh, J Michael; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2015-12-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection.

  4. [Drugs used to treat nicotine addiction].

    PubMed

    Zieleń, Iwona; Sliwińska-Mossoń, Mariola; Milnerowicz, Halina

    2012-01-01

    Tobacco smoking in Poland is fairly widespread on a large scale. Research suggests that the early twenty-first century, the percentage of female daily smokers aged 20 and above was 26%, and men the same age 43%. In addition, epidemiological studies have shown that smoking was the cause of approximately sixty-nine thousand deaths in Poland (including fifty-seven thousand men and twelve thousand women). It is common ground that cigarette smoking has a negative effect on our body. It represents one of the main and most commonly defined risk factors for many diseases that can be eliminated. Smoking often leads to addiction, and nicotine is an addictive drug. Nicotine addiction is characterized by symptoms such as: "hunger" smoking, difficulty in controlling behavior on smoking or the number of cigarettes smoked, nicotine withdrawal, the occurrence of tolerance, neglect of interests, as well as devoting more time on activities related to smoking, follow-up smoking despite knowledge of its dangers. The most commonly used in Poland, a questionnaire to identify nicotine dependence is a test Fagerstöma. Currently assigned some importance, "the doctor a conversation the patient" and motivating him to stop smoking and maintain abstinence as long as possible. But beyond the "conversation" is also used as an aid to medical treatment for the patient to stop smoking, especially to alleviate withdrawal symptoms. The first attempts of pharmacological help in the effort to weaning from smoking began in the thirties. Were conducted fairly successful, although uncontrolled trials with lobeline, an alkaloid of action similar to nicotine. In Poland, the drugs of first choice in the treatment of nicotine dependence are nicotine replacement therapies (nicotine gum and patches that contain nicotine) and bupropion SR. Quite a popular drugs to help in the fight against addiction are also cytisine and varenicline. The choice of the drug is usually the result of medical experience in the use

  5. EFFECTS OF D-CYCLOSERINE ON CUE-INDUCED CRAVING AND CIGARETTE SMOKING AMONG CONCURRENT COCAINE- AND NICOTINE-DEPENDENT VOLUNTEERS

    PubMed Central

    Yoon, Jin H.; Newton, Thomas F.; Haile, Colin N.; Bordnick, Patrick S.; Fintzy, Rachel E.; Culbertson, Chris; Mahoney, James J.; Hawkins, Rollin Y.; LaBounty, Kathleen R.; Ross, Elizabeth L.; Aziziyeh, Adel I.; De La Garza, Richard

    2012-01-01

    Rates of cigarette smoking are 3- to 4-fold greater among those with cocaine-dependence, and compared to non-users, cocaine users are at greater risk of incurring smoking-related negative health effects and death. The current study examined D-cycloserine’s (0 or 50 mg once weekly) 2) effects on 1) extinction of cue-induced craving for cigarettes, 2) cigarette smoking in conjunction with cognitive-behavioral therapy, and 3) safety and tolerability in cocaine-dependent smokers. This was a double-blind, placebo-controlled, between groups, outpatient study. Participants (N=29) were concurrent cocaine- and nicotine-dependent volunteers seeking treatment for their cigarette smoking. Study visits were 3 times per week for 4 consecutive weeks. At each visit, participants received cognitive-behavioral therapy for smoking, were exposed to smoking cues. A subset of participants (N=22) returned for 6-month follow-up visits. While craving decreased, no significant effects of D-cycloserine treatment were observed. Likewise, significant decreases in smoking were observed at study days 6 (p <0.002) and 12 (p <0.0001) relative to baseline, although no participants achieved complete abstinence. However, there was no effect of D-cycloserine on cigarette smoking during treatment or at 6-mos follow-up. The treatment was safe and tolerable, with nearly 90% of treatment sessions attended based on an intent-to-treat analysis. While no effects of D-cycloserine on craving or smoking were observed in the current study, the results do suggest smoking treatment is well accepted and may be effective for cocaine-dependent individuals. PMID:22560371

  6. Addressing the evidence for FDA nicotine replacement therapy label changes: a policy statement of the Association for the Treatment of Tobacco use and Dependence and the Society for Research on Nicotine and Tobacco.

    PubMed

    Fucito, Lisa M; Bars, Matthew P; Forray, Ariadna; Rojewski, Alana M; Shiffman, Saul; Selby, Peter; West, Robert; Foulds, Jonathan; Toll, Benjamin A

    2014-07-01

    Cigarette smoking creates a substantial public health burden. Identifying new, effective smoking cessation interventions that optimize existing interventions and promoting effective use of approved medications is a priority. When used as directed, nicotine replacement therapy (NRT) aids smoking cessation, but there is opportunity for improving its effectiveness. Until recently, NRT use guidelines advised smokers to begin using NRT on their quit date, only to use 1 NRT formulation at a time, to refrain from using NRT while smoking, and to stop NRT within 3 months regardless of progress. The Food and Drug Administration (FDA) issued a recent announcement allowing for NRT labeling changes with applications from pharmaceutical companies for such changes, and we applaud this decision. Nevertheless, additional revisions are warranted by current research. There is robust evidence that combining a longer-acting form (e.g., patch) with a shorter-acting form (e.g., lozenge) is more effective than NRT monotherapy and is safe. Moreover, extant evidence suggests that NRT use prior to a quit attempt or for smoking reduction as part of a quit attempt is safe and as effective as starting NRT on quit date. Specifically, prequit nicotine patch increases quit rates and may engage additional recalcitrant smokers. Last, NRT use longer than 3 months is safe and may be beneficial for relapse prevention in some smokers. This report summarizes the FDA announcement, reviews the evidence for further revisions to current FDA NRT guidelines, and makes recommendations for over-the-counter (OTC) NRT labeling to allow for (1) combined use of faster-acting NRT medications with nicotine patch, (2) nicotine patch use prior to quit date or NRT for smoking reduction as part of a quit attempt, and (3) prolonged NRT for up to 6 months without healthcare provider consultation. PMID:24919399

  7. Self-reported smoking effects and comparative value between cigarettes and high dose e-cigarettes in nicotine-dependent cigarette smokers.

    PubMed

    McPherson, Sterling; Howell, Donelle; Lewis, Jennifer; Barbosa-Leiker, Celestina; Bertotti Metoyer, Patrick; Roll, John

    2016-04-01

    The objective of this experiment was to evaluate the comparative value of cigarettes versus high dose e-cigarettes among nicotine-dependent cigarette smokers when compared with money or use of their usual cigarette brand. The experiment used a within-subject design with four sessions. After baseline assessment, participants attended two 15-min unrestricted smoking sessions: one cigarette smoking session and one e-cigarette smoking session. Participants then attended two multiple-choice procedure (MCP) sessions: a session comparing cigarettes and money and a session comparing e-cigarettes and money. Participants (n=27) had used cigarettes regularly, had never used e-cigarettes, and were not currently attempting to quit smoking. The sample consisted primarily of males (72%), with a mean age of 34 years. When given the opportunity to choose between smoking a cigarette or an e-cigarette, participants chose the cigarette 73.9% of the time. Findings from the MCP demonstrated that after the first e-cigarette exposure sessions, the crossover value for cigarettes ($3.45) was significantly higher compared with the crossover value for e-cigarettes ($2.73). The higher participant preference, self-reported smoking effects, and higher MCP crossover points indicate that cigarettes have a higher comparative value than high dose e-cigarettes among e-cigarette naive smokers.

  8. Integrated Prevention of Social Dependencies in Adolescents through the Scenario Method

    ERIC Educational Resources Information Center

    Maznichenko, Marina A.; Neskoromnykh, Nataliya I.

    2015-01-01

    This article provides a rationale for the need to take an integrated approach to prevention of social dependencies in adolescents. Through this approach, the authors fine-tune the determination of the phenomenon of prevention of social dependencies. The authors bring to light the potential of the scenario method in resolving the above objective.…

  9. Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

    PubMed

    de Kloet, Sybren F; Mansvelder, Huibert D; De Vries, Taco J

    2015-10-15

    Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are found in most brain regions, many studies on addiction have focused on the mesolimbic system and its reported behavioral correlates such as reward processing and reinforcement learning. Profound modulatory cholinergic input from the pedunculopontine and laterodorsal tegmentum to dopaminergic midbrain nuclei as well as local cholinergic interneuron projections to dopamine neuron axons in the striatum may play a major role in the effects of nicotine. Moreover, an indirect mesocorticolimbic feedback loop involving the medial prefrontal cortex may be involved in behavioral characteristics of nicotine addiction. Therefore, this review will highlight current understanding of the effects of nicotine on the function of mesolimbic and mesocortical dopamine projections in the mesocorticolimbic circuit. PMID:26208783

  10. [Behavioral characteristics of nicotine seeking: a role of the nicotine-conditioned effects and other mechanisms].

    PubMed

    Itasaka, Michio; Hironaka, Naoyuki; Miyata, Hisatsugu

    2015-06-01

    Nicotine dependence and its neural mechanisms have been well documented by pharmacological, behavioral and neuroscience studies. In this review, we introduce recent new findings in this theme, particularly on the role of nicotine -associated stimuli as non-pharmacological factors affecting maintaining/reinstating nicotine seeking. By using the techniques of drug self-administration and conditioned place preference, nicotine's specific property of forming seeking/taking behavior is well characterized, and the mechanisms of seeking/taking could be partly explained by discrete and/or contextual conditioned stimuli (dCS and cCS). After having the repeated Pavlovian conditioning in the training/conditioning sessions, CSs begin to play a key role for eliciting nicotine seeking behavior, with the activation of mesolimbic dopaminergic systems. In our study, intracranial self- stimulation (ICSS) was used to assess the mesolimbic dopamine activity. The nicotine-associated cCS also activated this neural system, which resulted in decreasing the ICSS threshold approximately 20% in the testing session under the cCS presentation. This finding would support the evidence of CS-induced incentive motivation for nicotine. According to the incentive salience hypothesis, the mesolimbic dopamine reflects the motivation elicited by incentives (CSs), and induces the drug seeking behavior, which is activated through amygdala--nucleus accumbens--medial prefrontal cortex circuit. Additionally, human brain imaging studies have revealed that tobacco- associated stimuli activate not only these regions, but also right temporo-parietal junction of human cortex, which is relevant to the visual attention. In summary, the above evidence shows that nicotine-conditioned stimuli might have powerful incentive salience and regulate nicotine seeking/taking behavior in animals and humans, though stress and nicotine-withdrawal could also enhance nicotine taking in the same way as other dependence -producing

  11. [Behavioral characteristics of nicotine seeking: a role of the nicotine-conditioned effects and other mechanisms].

    PubMed

    Itasaka, Michio; Hironaka, Naoyuki; Miyata, Hisatsugu

    2015-06-01

    Nicotine dependence and its neural mechanisms have been well documented by pharmacological, behavioral and neuroscience studies. In this review, we introduce recent new findings in this theme, particularly on the role of nicotine -associated stimuli as non-pharmacological factors affecting maintaining/reinstating nicotine seeking. By using the techniques of drug self-administration and conditioned place preference, nicotine's specific property of forming seeking/taking behavior is well characterized, and the mechanisms of seeking/taking could be partly explained by discrete and/or contextual conditioned stimuli (dCS and cCS). After having the repeated Pavlovian conditioning in the training/conditioning sessions, CSs begin to play a key role for eliciting nicotine seeking behavior, with the activation of mesolimbic dopaminergic systems. In our study, intracranial self- stimulation (ICSS) was used to assess the mesolimbic dopamine activity. The nicotine-associated cCS also activated this neural system, which resulted in decreasing the ICSS threshold approximately 20% in the testing session under the cCS presentation. This finding would support the evidence of CS-induced incentive motivation for nicotine. According to the incentive salience hypothesis, the mesolimbic dopamine reflects the motivation elicited by incentives (CSs), and induces the drug seeking behavior, which is activated through amygdala--nucleus accumbens--medial prefrontal cortex circuit. Additionally, human brain imaging studies have revealed that tobacco- associated stimuli activate not only these regions, but also right temporo-parietal junction of human cortex, which is relevant to the visual attention. In summary, the above evidence shows that nicotine-conditioned stimuli might have powerful incentive salience and regulate nicotine seeking/taking behavior in animals and humans, though stress and nicotine-withdrawal could also enhance nicotine taking in the same way as other dependence -producing

  12. Effects of chronic buspirone treatment on nicotine and concurrent nicotine+cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J

    2013-06-01

    Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal pharmacotherapy would reduce both cigarette smoking and cocaine abuse. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on serotonin and dopamine systems. In preclinical studies, it reduced cocaine self-administration following both acute and chronic treatment in rhesus monkeys. The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of intravenous (IV) nicotine and IV nicotine+cocaine combinations. Five cocaine-experienced adult rhesus monkeys (Macaca mulatta) were trained to self-administer nicotine or nicotine+cocaine combinations, and food pellets (1 g) during four 1-h daily sessions under a second-order schedule of reinforcement (FR 2 (VR16:S)). Each nicotine+cocaine combination maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Buspirone (0.032-0.56 mg/kg/h) was administered IV through one lumen of a double-lumen catheter every 20 min for 23 h each day, for 7-10 consecutive days. Each 7-10-day sequence of buspirone treatment was followed by saline-control treatment for at least 3 days until food- and drug-maintained responding returned to baseline. Buspirone dose-dependently reduced responding maintained by nicotine alone (0.001-0.1 mg/kg/inj; P<0.01) and by nicotine (0.001 or 0.0032 mg/kg/inj)+cocaine combinations (0.0032 mg/kg/inj; P<0.05-0.001) with no significant effects on food-maintained responding. We conclude that buspirone selectively attenuates the reinforcing effects of nicotine alone and nicotine+cocaine polydrug combinations in a nonhuman primate model of drug self-administration. PMID:23337868

  13. The audience effect in adolescence depends on who's looking over your shoulder

    PubMed Central

    Wolf, Laura K.; Bazargani, Narges; Kilford, Emma J.; Dumontheil, Iroise; Blakemore, Sarah-Jayne

    2015-01-01

    Adolescents have been shown to be particularly sensitive to peer influence. However, the data supporting these findings have been mostly limited to the impact of peers on risk-taking behaviours. Here, we investigated the influence of peers on performance of a high-level cognitive task (relational reasoning) during adolescence. We further assessed whether this effect on performance was dependent on the identity of the audience, either a friend (peer) or the experimenter (non-peer). We tested 24 younger adolescent (10.6–14.2 years), 20 older adolescent (14.9–17.8 years) and 20 adult (21.8–34.9 years) female participants. The presence of an audience affected adolescent, but not adult, relational reasoning performance. This audience effect on adolescent performance was influenced by the participants' age, task difficulty and the identity of the audience. These findings may have implications for education, where adolescents often do classwork or homework in the presence of others. PMID:26043167

  14. The audience effect in adolescence depends on who's looking over your shoulder.

    PubMed

    Wolf, Laura K; Bazargani, Narges; Kilford, Emma J; Dumontheil, Iroise; Blakemore, Sarah-Jayne

    2015-08-01

    Adolescents have been shown to be particularly sensitive to peer influence. However, the data supporting these findings have been mostly limited to the impact of peers on risk-taking behaviours. Here, we investigated the influence of peers on performance of a high-level cognitive task (relational reasoning) during adolescence. We further assessed whether this effect on performance was dependent on the identity of the audience, either a friend (peer) or the experimenter (non-peer). We tested 24 younger adolescent (10.6-14.2 years), 20 older adolescent (14.9-17.8 years) and 20 adult (21.8-34.9 years) female participants. The presence of an audience affected adolescent, but not adult, relational reasoning performance. This audience effect on adolescent performance was influenced by the participants' age, task difficulty and the identity of the audience. These findings may have implications for education, where adolescents often do classwork or homework in the presence of others. PMID:26043167

  15. Prenatal nicotine exposure alters the types of nicotinic receptors that facilitate excitatory inputs to cardiac vagal neurons.

    PubMed

    Huang, Zheng-Gui; Wang, Xin; Evans, Cory; Gold, Allison; Bouairi, Evguenia; Mendelowitz, David

    2004-10-01

    Nicotinic receptors play an important role in modulating the activity of parasympathetic cardiac vagal neurons in the medulla. Previous work has shown nicotine acts via at least three mechanisms to excite brain stem premotor cardiac vagal neurons. Nicotine evokes a direct increase in holding current and facilitates both the frequency and amplitude of glutamatergic neurotransmission to cardiac vagal neurons. This study tests whether these nicotinic receptor-mediated responses are endogenously active, whether alpha4beta2 and alpha7 nicotinic receptors are involved, and whether prenatal exposure to nicotine alters the magnitude of these responses and the types of nicotinic receptors involved. Application of neostigmine (10 microM) significantly increased the holding current, amplitude, and frequency of miniature excitatory postsynaptic current (mEPSC) glutamatergic events in cardiac vagal neurons. In unexposed animals, the nicotine-evoked facilitation of mEPSC frequency, but not mEPSC amplitude or holding current, was blocked by alpha-bungarotoxin (100 nM). Prenatal nicotine exposure significantly exaggerated and altered the types of nicotinic receptors involved in these responses. In prenatal nicotine-exposed animals, alpha-bungarotoxin only partially reduced the increase in mEPSC frequency. In addition, in prenatal nicotine-exposed animals, the increase in holding current was partially dependent on alpha-7 subunit-containing nicotinic receptors, in contrast to unexposed animals in which alpha-bungarotoxin had no effect. These results indicate prenatal nicotine exposure, one of the highest risk factors for sudden infant death syndrome (SIDS), exaggerates the responses and changes the types of nicotinic receptors involved in exciting premotor cardiac vagal neurons. These alterations could be responsible for the pronounced bradycardia that occurs during apnea in SIDS victims.

  16. Social and Psychological Factors of Drug Abuse Among Children and Adolescents.

    ERIC Educational Resources Information Center

    Barter, James T.; Werme, Paul H.

    This paper is devoted to a selected review of literature on drug abuse and dependence among children and adolescents. It is divided into seven sections, each giving information on studies, both nationally and internationally, on a particular drug. These are: nicotine, alcohol, organic solvents (sniffing of substances such as plastic cement, laquer…

  17. The Prevalence and Determinants of Tobacco Use among Adolescents in Saudi Arabia

    ERIC Educational Resources Information Center

    Al Agili, Dania E.; Park, Hyoun-Kyoung

    2012-01-01

    Background: Adolescent tobacco use has been a serious public health issue, resulting in longer duration of tobacco use and higher nicotine dependence in adulthood. This study identified the current status of tobacco use among middle schools students in Jeddah, Saudi Arabia and the factors leading to tobacco use, to provide information on how to…

  18. Validation of the Waterpipe Tolerance Questionnaire among Jordanian School-Going Adolescent Waterpipe Users

    PubMed Central

    Alzyoud, Sukaina; Veeranki, Sreenivas P.; Kheirallah, Khalid A.; Shotar, Ali M.; Pbert, Lori

    2016-01-01

    Introduction: Waterpipe use among adolescents has been increasing progressively. Yet no studies were reported to assess the validity and reliability of nicotine dependence scale. The current study aims to assess the validity and reliability of an Arabic version of the modified Waterpipe Tolerance Questionnaire WTQ among school-going adolescent waterpipe users. Methods: In a cross-sectional study conducted in Jordan, information on waterpipe use among 333 school-going adolescents aged 11-18 years was obtained using the Arabic version of the WTQ. An exploratory factor analysis and correlation matrices were conducted to assess validity and reliability of the WTQ. Results: The WTQ had a 0.73 alpha of internal consistency indicating moderate level of reliability. The scale showed multidimensionality with items loading on two factors, namely waterpipe consumption and morning smoking. Conclusion: This study report nicotine dependence level among school-going adolescents who identify themselves as waterpipe users using the WTQ. PMID:26383198

  19. Cortical control of VTA function and influence on nicotine reward.

    PubMed

    Wu, Jie; Gao, Ming; Shen, Jian-Xin; Shi, Wei-Xing; Oster, Andrew M; Gutkin, Boris S

    2013-10-15

    Tobacco use is a major public health problem. Nicotine acts on widely distributed nicotinic acetylcholine receptors (nAChRs) in the brain and excites dopamine (DA) neurons in the ventral tegmental area (VTA). The elicited increase of DA neuronal activity is thought to be an important mechanism for nicotine reward and subsequently the transition to addiction. However, the current understanding of nicotine reward is based predominantly on the data accumulated from in vitro studies, often from VTA slices. Isolated VTA slices artificially terminate communications between neurons in the VTA and other brain regions that may significantly alter nicotinic effects. Consequently, the mechanisms of nicotinic excitation of VTA DA neurons under in vivo conditions have received only limited attention. Building upon the existing knowledge acquired in vitro, it is now time to elucidate the integrated mechanisms of nicotinic reward on intact systems that are more relevant to understanding the action of nicotine or other addictive drugs. In this review, we summarize recent studies that demonstrate the impact of prefrontal cortex (PFC) on the modulation of VTA DA neuronal function and nicotine reward. Based on existing evidence, we propose a new hypothesis that PFC-VTA functional coupling serves as an integration mechanism for nicotine reward. Moreover, addiction may develop due to nicotine perturbing the PFC-VTA coupling and thereby eliminating the PFC-dependent cognitive control over behavior.

  20. Nicotine enhancement of dopamine release by a calcium-dependent increase in the size of the readily releasable pool of synaptic vesicles.

    PubMed

    Turner, Timothy J

    2004-12-15

    A major factor underlying compulsive tobacco use is nicotine-induced modulation of dopamine release in the mesolimbic reward pathway (Wise and Rompre, 1989). An established biochemical mechanism for nicotine-enhanced dopamine release is by activating presynaptic nicotinic acetylcholine receptors (nAChRs) (Wonnacott, 1997). Prolonged application of 10(-7) to 10(-5) m nicotine to striatal synaptosomes promoted a sustained efflux of [3H]dopamine. This nicotine effect was mediated by non-alpha7 nAChRs, because it was blocked by 5 mum mecamylamine but was resistant to 100 nm alpha-bungarotoxin (alphaBgTx). Dopamine release was diminished by omitting Na+ or by applying peptide calcium channel blockers, indicating that nAChRs trigger release by depolarizing the nerve terminals. However, because alpha7 receptors rapidly desensitize in the continuous presence of agonists, a repetitive stimulation protocol was used to evaluate the possible significance of desensitization. This protocol produced a transient increase in [3H]dopamine released by depolarization and a significant increase in the response to hypertonic solutions that measure the size of the readily releasable pool (RRP) of synaptic vesicles. The nicotine-induced increase in the size of the readily releasable pool was blocked by alphaBgTx and by the calmodulin antagonist calmidazolium, suggesting that Ca2+ entry through alpha7 nAChRs specifically enhances synaptic vesicle mobilization at dopamine terminals. Thus, nicotine enhances dopamine release by two complementary actions mediated by discrete nAChR subtypes and suggest that the alpha7 nAChR-mediated pathway is tightly and specifically coupled to refilling of the RRP of vesicles in dopamine terminals.

  1. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence

    PubMed Central

    Shaw, Daniel S.; Sitnick, Stephanie L.; Musselman, Samuel C.; Forbes, Erika E.

    2015-01-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function. PMID:24795442

  2. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence.

    PubMed

    Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E

    2015-03-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.

  3. Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner.

    PubMed

    Freund, Ronald K; Graw, Sharon; Choo, Kevin S; Stevens, Karen E; Leonard, Sherry; Dell'Acqua, Mark L

    2016-08-01

    Reduced α7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the α7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance. Thus, we compared the consequences of knocking out the α7nAChR on synaptic plasticity in C57/Bl6 and C3H mice, which differ in their basal α7nAChR expression levels. Homozygous α7 deletion in C3H mice, which normally express higher α7nAChR levels, resulted in impaired long-term potentiation (LTP) at hippocampal CA1 synapses, while C3H α7 heterozygous mice maintained robust LTP. In contrast, homozygous α7 deletion in C57 mice, which normally express lower α7nAChR levels, did not alter LTP, as had been previously reported for this strain. Thus, the threshold of Chrna7 expression required for LTP may be different in the two strains. Measurements of auditory gating, a hippocampal-dependent behavioral paradigm used to identify schizophrenia-associated sensory processing deficits, was abnormal in C3H α7 knockout mice confirming that auditory gating also requires α7nAChR expression. Our studies highlight the importance of genetic background on the regulation of synaptic plasticity and could be relevant for understanding genetic and cognitive heterogeneity in human studies of α7nAChR dysfunction in mental disorders.

  4. Effect of the use-dependent, nicotinic receptor antagonist BTMPS in the forced swim test and elevated plus maze after cocaine discontinuation in rats.

    PubMed

    Hall, Brandon J; Pearson, Laura S; Buccafusco, Jerry J

    2010-04-26

    Withdrawal from cocaine use often is associated with anxiety and depressive states. In this study the use-dependent, nicotinic acetylcholine receptor antagonist bis-(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was studied for its ability to reduce these symptoms in two rat models of anxiety and depression. Rats were administered saline vehicle, or two escalating doses of cocaine, for a period of 5 days and they were evaluated during the period after cocaine discontinuation in the elevated plus maze (anxiety) and the forced swim test (affect). BTMPS (0.25, 0.5, or 0.75mg/kg) was co-administered with saline or cocaine in the dependence phase. Withdrawal from cocaine administration alone resulted in reductions in both the time spent in the open arms of the elevated plus maze test, as well as entries into, and out of, the open arms of the maze. Withdrawal from cocaine also resulted in a reduction of escape behaviors, and the time to first immobility, in the forced swim test. Treatment with BTMPS produced a reversal of cocaine-induced anxiety-like behaviors in the elevated plus maze, including an increase (up to 68%) in time spent in the open arms of the maze and an increase in the number of crossings between open and enclosed arms. BTMPS also reduced depressive-like behaviors associated with the forced swim test, including up to a 62% increase in the time to first immobility and a 50% increase in escape behavior. These results provide proof of concept for the development and use of cholinergic compounds in the treatment of substance abuse. PMID:20226229

  5. Effect of the use-dependent, nicotinic receptor antagonist BTMPS in the forced swim test and elevated plus maze after cocaine discontinuation in rats.

    PubMed

    Hall, Brandon J; Pearson, Laura S; Buccafusco, Jerry J

    2010-04-26

    Withdrawal from cocaine use often is associated with anxiety and depressive states. In this study the use-dependent, nicotinic acetylcholine receptor antagonist bis-(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was studied for its ability to reduce these symptoms in two rat models of anxiety and depression. Rats were administered saline vehicle, or two escalating doses of cocaine, for a period of 5 days and they were evaluated during the period after cocaine discontinuation in the elevated plus maze (anxiety) and the forced swim test (affect). BTMPS (0.25, 0.5, or 0.75mg/kg) was co-administered with saline or cocaine in the dependence phase. Withdrawal from cocaine administration alone resulted in reductions in both the time spent in the open arms of the elevated plus maze test, as well as entries into, and out of, the open arms of the maze. Withdrawal from cocaine also resulted in a reduction of escape behaviors, and the time to first immobility, in the forced swim test. Treatment with BTMPS produced a reversal of cocaine-induced anxiety-like behaviors in the elevated plus maze, including an increase (up to 68%) in time spent in the open arms of the maze and an increase in the number of crossings between open and enclosed arms. BTMPS also reduced depressive-like behaviors associated with the forced swim test, including up to a 62% increase in the time to first immobility and a 50% increase in escape behavior. These results provide proof of concept for the development and use of cholinergic compounds in the treatment of substance abuse.

  6. alpha4beta2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief

    PubMed Central

    McGranahan, Tresa M.; Patzlaff, Natalie E.; Grady, Sharon R.; Heinemann, Stephen F.; Booker, T.K.

    2012-01-01

    Nicotine is the primary psychoactive substance in tobacco and it exerts its effects by interaction with various subtypes of nicotinic acetylcholine receptors (nAChRs) in the brain. One of the major subtypes expressed in brain, the alpha4beta2-nAChR, endogenously modulates neuronal excitability and thereby, modifies certain normal, as well as nicotine-induced, behaviors. Although alpha4-containing nAChRs are widely expressed across the brain, a major focus has been on their roles within midbrain dopaminergic regions involved in drug addition, mental illness and movement control in humans. We developed a unique model system to examine the role of alpha4-nAChRs within dopaminergic neurons by a targeted genetic deletion of the alpha4 subunit from dopaminergic neurons in mice. The loss alpha4 mRNA and alpha4beta2-nAChRs from dopaminergic neurons was confirmed, as well as selective loss of alpha4beta2-nAChR function from dopaminergic but not GABAergic neurons. Two behaviors central to nicotine dependence, reward and anxiety relief, were examined. Alpha4-nAChRs specifically on dopaminergic neurons were demonstrated to be necessary for nicotine reward as measured by nicotine place preference, but not for another drug of addiction, cocaine. Alpha4-nAChRs are necessary for the anxiolytic effects of nicotine in the elevated plus maze and elimination of alpha4-beta2-nAChRs specifically from dopaminergic neurons decreased sensitivity to the anxiolytic effects of nicotine. Deletion of alpha4-nAChRs specifically from dopaminergic neurons also increased sensitivity to nicotine-induced locomotor depression, however nicotine-induced hypothermia was unaffected. This is the first work to develop a dopaminergic specific deletion of a nAChR subunit and examine resulting changes in nicotine behaviors. PMID:21795541

  7. Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

    2014-04-01

    Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine. PMID:24304823

  8. Decaffeinated Coffee and Nicotine-Free Tobacco Provide Neuroprotection in Drosophila Models of Parkinson's Disease through an NRF2-Dependent Mechanism

    PubMed Central

    Trinh, Kien; Andrews, Laurie; Krause, James; Hanak, Tyler; Lee, Daewoo; Gelb, Michael

    2010-01-01

    Epidemiological studies have revealed a significantly reduced risk of Parkinson's disease (PD) among coffee and tobacco users, although it is unclear whether these correlations reflect neuroprotective/symptomatic effects of these agents or preexisting differences in the brains of tobacco and coffee users. Here, we report that coffee and tobacco, but not caffeine or nicotine, are neuroprotective in fly PD models. We further report that decaffeinated coffee and nicotine-free tobacco are as neuroprotective as their caffeine and nicotine-containing counterparts and that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco are also evident in Drosophila models of Alzheimer's disease and polyglutamine disease. Finally, we report that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco require the cytoprotective transcription factor Nrf2 and that a known Nrf2 activator in coffee, cafestol, is also able to confer neuroprotection in our fly models of PD. Our findings indicate that coffee and tobacco contain Nrf2-activating compounds that may account for the reduced risk of PD among coffee and tobacco users. These compounds represent attractive candidates for therapeutic intervention in PD and perhaps other neurodegenerative diseases. PMID:20410106

  9. REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

    2015-01-01

    Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

  10. [Nicotine effects on mitochondria membrane potential: participation of nicotinic acetylcholine receptors].

    PubMed

    Gergalova, G L; Skok, M V

    2011-01-01

    The effect of nicotine on the mouse liver mitochondria was studied by fluorescent flow cytometry. Mice consumed nicotine during 65 days; alternatively, nicotine was added to isolated mitochondria. Mitochondria of nicotine-treated mice had significantly lower basic levels of membrane potential and granularity as compared to those of the control group. Pre-incubation of the isolated mitochondria with nicotine prevented from dissipation of their membrane potential stimulated with 0.8 microM CaCl2 depending on the dose, and this effect was strengthened by the antagonist of alpha7 nicotinic receptors (alpha7 nAChR) methyllicaconitine. Mitochondria of mice intravenously injected with the antibodies against alpha7 nAChR demonstrated lower levels of membrane potential. Introduction of nicotine, choline, acetylcholine or synthetic alpha7 nAChR agonist PNU 282987 into the incubation medium inhibited Ca2+ accumulation in mitochondria, although the doses of agonists were too low to activate the alpha7 nAChR ion channel. It is concluded that nicotine consumption worsens the functional state of mitochondria by affecting their membrane potential and granularity, and this effect, at least in part, is mediated by alpha7 nAChR desensitization.

  11. From child maltreatment to adolescent cannabis abuse and dependence: A developmental cascade model

    PubMed Central

    Rogosch, Fred A.; Oshri, Assaf; Cicchetti, Dante

    2010-01-01

    A developmental cascade model tested associations among child maltreatment, internalizing and externalizing psychopathology, social competence, and cannabis abuse and dependence symptoms in a longitudinal cohort (N = 415). Nested structural equation models evaluated continuity and cross-domain influences among broad multi-informant constructs across four developmental periods: age 7 to 9, 10 to 12, 13 to 15, and 15 to 18. Results indicated significant paths from child maltreatment to early externalizing and internalizing problems and social competence, as well as to cannabis abuse and dependence (CAD) symptoms in adolescence. Youth CAD symptoms were primarily related directly to child maltreatment and externalizing problems. Childhood internalizing symptoms contributed to later childhood decreases in social competence, which predicted increases in late adolescent externalizing problems. Using a developmental psychopathology framework, results are discussed in relation to cascade and transactional effects and the interplay between problem behaviors during childhood and development of CAD symptoms during early and late adolescence. PMID:20883588

  12. [Reconsideration of nicotine and other substance dependence: a clue from dependence-related mentation including reward, motivation, learning, delusion and hallucination toward understanding the concept of non-substance-related addiction].

    PubMed

    Miyata, Hisatsugu

    2013-11-01

    Nicotine produces core symptoms of substance dependence (craving and withdrawal) without any psychotic symptoms. The psychopharmacological structure of craving is hypothesized to be constituted by three components: the primary reinforcing property of a substance, the secondary reinforcing property of that substance (conditioned aspects of the environment, such as contextual or specific cues associated with substance taking), and the negative affective motivational property during withdrawal (i.e. the desire to avoid the dysphoric withdrawal symptoms elicits craving). Among the three components, the primary reinforcing property of a substance forms the most fundamental factor for establishing substance dependence. Sensitization or reverse tolerance observed in locomotor activity of animals, which had been believed to be a methamphetamine psychosis model, is demonstrated to reflect the establishment of conditioned reinforcement. Finally, non-substance-related addiction such as gambling, internet, and sex is discussed. From the aspect of the above hypothetical psychopharmacological structure of craving, the most significant difference between substance dependence and non-substance-related addiction is that the primary reinforcing property of non-substance reward is relatively intangible in comparison with that of a substance of abuse.

  13. Hormones, nicotine, and cocaine: clinical studies.

    PubMed

    Mello, Nancy K

    2010-06-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (<20 min), ratings of "high" and "rush" began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.

  14. Nicotine-morphine interactions at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors.

    PubMed

    Talka, Reeta; Salminen, Outi; Whiteaker, Paul; Lukas, Ronald J; Tuominen, Raimo K

    2013-02-15

    Nicotine and opioids share several behavioral and rewarding properties. Although both opioids and nicotine have their own specific mechanism of action, there is empirical and experimental evidence of interactions between these drugs. We studied receptor-level interactions of nicotine and morphine at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors. [(3)H]epibatidine displacement was used to determine if morphine binds competitively to nicotinic acetylcholine receptors. Functional interactions of morphine and nicotine were studied with calcium fluorometry and (86)Rb(+) efflux assays. Morphine displaced [(3)H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2μM in SH-EP1-hα4β2 cells, 0.16μM and 126μM in SH-SY5Y cells and 43.7μM in SH-EP1-hα7 cells. In SH-EP1-hα4β2 cells expressing α4β2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of (86)Rb(+) efflux comparable to cytisine (with EC50 values of 53.3μM for morphine and 5.38μM for cytisine). The effect of morphine was attenuated concentration-dependently by the nicotinic antagonist mecamylamine. In the SH-SY5Y cell line expressing several subtypes of nicotinic acetylcholine receptors morphine had an inhibitory effect on nicotine induced (86)Rb(+) ion efflux mediated by α3(⁎) nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at α4β2 nicotinic acetylcholine receptors and as a weak antagonist at α3(⁎) nicotinic acetylcholine receptors.

  15. Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults.

    PubMed

    Abramoff, Benjamin A; Lange, Hannah L H; Matson, Steven C; Cottrill, Casey B; Bridge, Jeffrey A; Abdel-Rasoul, Mahmoud; Bonny, Andrea E

    2015-01-01

    Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence.

  16. Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults

    PubMed Central

    Abramoff, Benjamin A.; Lange, Hannah L. H.; Matson, Steven C.; Cottrill, Casey B.; Bridge, Jeffrey A.; Abdel-Rasoul, Mahmoud; Bonny, Andrea E.

    2015-01-01

    Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence. PMID:26664819

  17. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Stadler, Ashley; Levin, Edward D; Seidler, Frederic J

    2015-09-01

    Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage.

  18. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Stadler, Ashley; Levin, Edward D; Seidler, Frederic J

    2015-09-01

    Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage. PMID:26085346

  19. Risky Decision Making in Substance Dependent Adolescents with a Disruptive Behavior Disorder

    ERIC Educational Resources Information Center

    Schutter, Dennis J. L. G.; van Bokhoven, Irene; Vanderschuren, Louk J. M. J.; Lochman, John E.; Matthys, Walter

    2011-01-01

    Of all psychiatric disorders, the disruptive behavior disorders (DBDs) are the most likely to predispose to substance dependence (SD). One possible underlying mechanism for this increased vulnerability is risky decision making. The aim of this study was to examine decision making in DBD adolescents with and without SD. Twenty-five DBD adolescents…

  20. Neurotensin agonist attenuates nicotine potentiation to cocaine sensitization.

    PubMed

    Fredrickson, Paul; Boules, Mona; Stennett, Bethany; Richelson, Elliott

    2014-03-01

    Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a "gateway drug". Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine. PMID:25379267

  1. Sensation Seeking and Internet Dependence of Taiwanese High School Adolescents.

    ERIC Educational Resources Information Center

    Lin, Sunny S. J.; Tsai, Chin-Chung

    This paper presents the second year follow-up research on Internet addiction among Taiwanese high school students from surveys of 753 students. A psychological profile of users was determined in order to differentiate motivation of Internet dependence and non-dependence. Data was analyzed to establish whether sensation seeking was a part of…

  2. Mechanisms of Nicotine Addiction

    SciTech Connect

    McGehee, Daniel

    2002-06-26

    Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain's reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increase in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain's reward system.

  3. Mechanisms of Nicotine Addiction

    SciTech Connect

    McGehee, Daniel

    2009-06-26

    Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain’s reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increase in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain’s reward system.

  4. Risk factors for adolescent substance abuse and dependence: data from a national sample.

    PubMed

    Kilpatrick, D G; Acierno, R; Saunders, B; Resnick, H S; Best, C L; Schnurr, P P

    2000-02-01

    A national household probability sample of 4,023 adolescents aged 12 to 17 years was interviewed by telephone about substance use, victimization experiences, familial substance use, and posttraumatic reactions to identify risk factors for Diagnostic and Statistical Manual of Mental Disorders--(4th ed.; American Psychiatric Association, 1994) defined substance abuse/dependence. Age and ethnicity data were available for 3,907 participants. Major findings were (a) adolescents who had been physically assaulted, who had been sexually assaulted, who had witnessed violence, or who had family members with alcohol or drug use problems had increased risk for current substance abuse/dependence; (b) posttraumatic stress disorder independently increased risk of marijuana and hard drug abuse/dependence; and (c) when effects of other variables were controlled, African Americans, but not Hispanics or Native Americans, were at approximately 1/3 the risk of substance abuse/dependence as Caucasians.

  5. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

    PubMed

    Yoon, Jin H; Lane, Scott D; Weaver, Michael F

    2015-09-01

    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

  6. Nicotine induces DNA damage in human salivary glands.

    PubMed

    Ginzkey, Christian; Kampfinger, Katja; Friehs, Gudrun; Köhler, Christian; Hagen, Rudolf; Richter, Elmar; Kleinsasser, Norbert H

    2009-01-10

    The tobacco alkaloid nicotine is responsible for addiction to tobacco and supposed to contribute to tobacco carcinogensis, too. Recently, genotoxic effects of nicotine have been reported in human cells from blood and upper aerodigestive tract. Because of nicotine accumulation in saliva, the study of possible in vitro genotoxic effects of nicotine have been extended to human salivary gland cells. Specimens of parotid glands of 10 tumor patients were obtained from tumor-free tissue. Single cells were prepared by enzymatic digestion immediately after surgery and exposed for 1h to 0.125-4.0mM of nicotine. Possible genotoxic effects were determined by the Comet assay using the % DNA in tail (DT) as a reliable indicator of DNA damage. Nicotine induced a significant dose-dependent increase of DNA migration in parotid gland single-cells. The mean DT was 1.12-fold (0.125mM) to 2.24-fold (4.0mM) higher compared to control. The lowest concentration eliciting significant DNA damage within 1h, 0.25mM nicotine, is only 10-fold higher than maximal concentrations of nicotine reported in saliva after unrestricted smoking. Although conclusive evidence for a carcinogenic potential of nicotine is still lacking, the safety of long-term nicotine replacement therapy should be carefully monitored. PMID:18852035

  7. Reducing the nicotine content to make cigarettes less addictive.

    PubMed

    Benowitz, Neal L; Henningfield, Jack E

    2013-05-01

    Nicotine is highly addictive and is primarily responsible for the maintenance of cigarette smoking. In 1994, Benowitz and Henningfield proposed the idea of federal regulation of the nicotine content of cigarettes such that the nicotine content of cigarettes would be reduced over time, resulting in lower intake of nicotine and a lower level of nicotine dependence. When nicotine levels get very low, cigarettes would be much less addictive. As a result, fewer young people who experiment with cigarettes would become addicted adult smokers and previously addicted smokers would find it easier to quit smoking when they attempt to do so. The regulatory authority to promulgate such a public health strategy was provided by the Family Smoking Prevention and Tobacco Control Act. Although it precludes 'reducing nicotine to zero', the act does not prohibit the Food and Drug Administration from setting standards for cigarette nicotine content that would prevent them from being capable of causing addiction. This paper reviews the assumptions implicit in a nicotine reduction strategy, examines the available data on the feasibility and safety of nicotine reduction, and discusses the public education, surveillance and support services that would be needed for the implementation of such a policy.

  8. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

    PubMed

    Yoon, Jin H; Lane, Scott D; Weaver, Michael F

    2015-09-01

    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs. PMID:26375198

  9. Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence.

    PubMed

    McClernon, F Joseph; Conklin, Cynthia A; Kozink, Rachel V; Adcock, R Alison; Sweitzer, Maggie M; Addicott, Merideth A; Chou, Ying-hui; Chen, Nan-kuei; Hallyburton, Matthew B; DeVito, Anthony M

    2016-02-01

    Environments associated with prior drug use provoke craving and drug taking, and set the stage for lapse/relapse. Although the neurobehavioral bases of environment-induced drug taking have been investigated with animal models, the influence of drug-environments on brain function and behavior in clinical populations of substance users is largely unexplored. Adult smokers (n=40) photographed locations personally associated with smoking (personal smoking environments; PSEs) or personal nonsmoking environment (PNEs). Following 24-h abstinence, participants underwent fMRI scanning while viewing PSEs, PNEs, standard smoking and nonsmoking environments, as well as proximal smoking (eg, lit cigarette) and nonsmoking (eg, pencil) cues. Finally, in two separate sessions following 6-h abstinence they viewed either PSEs or PNEs while cue-induced self-reported craving and smoking behavior were assessed. Viewing PSEs increased blood oxygen level-dependent signal in right posterior hippocampus (pHPC; F(2,685)=3.74, p<0.024) and bilateral insula (left: F(2,685)=6.87, p=0.0011; right: F(2,685)=5.34, p=0.005). In the laboratory, viewing PSEs, compared with PNEs, was associated with higher craving levels (F(2,180)=18.32, p<0.0001) and greater ad lib smoking (F(1,36)=5.01, p=0.032). The effect of PSEs (minus PNEs) on brain activation in right insula was positively correlated with the effect of PSEs (minus PNEs) on number of puffs taken from a cigarette (r=0.6, p=0.001). Our data, for the first time in humans, elucidates the neural mechanisms that mediate the effects of real-world drug-associated environments on drug taking behavior under conditions of drug abstinence. These findings establish targets for the development and evaluation of treatments seeking to reduce environment provoked relapse.

  10. Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats.

    PubMed

    Hall, Brandon J; Wells, Corinne; Allenby, Cheyenne; Lin, Mung Yan; Hao, Ian; Marshall, Lindsey; Rose, Jed E; Levin, Edward D

    2014-05-01

    Tobacco smoking has been shown to be quite addictive in people. However, nicotine itself is a weak reinforcer compared to other commonly abused drugs, leading speculation that other factors contribute to the high prevalence of tobacco addiction in the human population. In addition to nicotine, there are over 5000 chemical compounds that have been identified in tobacco smoke, and more work is needed to ascertain their potential contributions to tobacco's highly addictive properties, or as potential candidates for smoking cessation treatment. In this study, we examined seven non-nicotine tobacco constituent compounds (anabasine, anatabine, nornicotine, myosmine, harmane, norharmane, and tyramine) for their effects on nicotine self-administration behavior in rats. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine (0.03 mg/kg/50 μl infusion) under a fixed ratio-1 schedule of reinforcement. Each self-administration session lasted 45 min. Doses of each tobacco constituent compound were administered subcutaneously 10 min prior to the start of each session in a repeated measures, counterbalanced order two times. Anabasine displayed a biphasic dose-effect function. Pretreatment with 0.02 mg/kg anabasine resulted in a 25% increase in nicotine self-administration, while 2.0mg/kg of anabasine reduced nicotine infusions per session by over 50%. Pretreatment with 2.0mg/kg anatabine also significantly reduced nicotine self-administration by nearly half. These results suggest that some non-nicotine tobacco constituents may enhance or reduce nicotine's reinforcing properties. Also, depending upon the appropriate dose, some of these compounds may also serve as potential smoking cessation agents. PMID:24560911

  11. Donepezil, an acetylcholinesterase inhibitor, attenuates nicotine self-administration and reinstatement of nicotine seeking in rats.

    PubMed

    Kimmey, Blake A; Rupprecht, Laura E; Hayes, Matthew R; Schmidt, Heath D

    2014-07-01

    Nicotine craving and cognitive impairments represent core symptoms of nicotine withdrawal and predict relapse in abstinent smokers. Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Donepezil is an acetylcholinesterase inhibitor that has been shown previously to improve cognition in healthy non-treatment-seeking smokers. However, there are no studies examining the effects of donepezil on nicotine self-administration and/or the reinstatement of nicotine-seeking behavior in rodents. The present experiments were designed to determine the effects of acute donepezil administration on nicotine taking and the reinstatement of nicotine-seeking behavior, an animal model of relapse in abstinent human smokers. Moreover, the effects of acute donepezil administration on sucrose self-administration and sucrose seeking were also investigated in order to determine whether donepezil's effects generalized to other reinforced behaviors. Acute donepezil administration (1.0 or 3.0 mg/kg, i.p.) attenuated nicotine, but not sucrose self-administration maintained on a fixed-ratio 5 schedule of reinforcement. Donepezil administration also dose-dependently attenuated the reinstatement of both nicotine- and sucrose-seeking behaviors. Commonly reported adverse effects of donepezil treatment in humans are nausea and vomiting. However, at doses required to attenuate nicotine self-administration in rodents, no effects of donepezil on nausea/malaise as measured by pica were observed. Collectively, these results indicate that increased extracellular acetylcholine levels are sufficient to attenuate nicotine taking and seeking in rats and that these effects are not due to adverse malaise symptoms such as nausea.

  12. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

  13. Maintenance and suppression of behavior by intravenous nicotine injections in squirrel monkeys.

    PubMed

    Goldberg, S R; Spealman, R D

    1982-02-01

    Nicotine appears to be a contributing factor in maintaining cigarette smoking, but experimental evidence for its reinforcing effects is scarce. Indeed, it has been suggested that in some situations nicotine may have noxious properties, which limit smoking behavior. These ideas were explored by comparing the effects of intravenous injections of nicotine on behavior of squirrel monkeys under two experimental procedures. Under a fixed-interval schedule of nicotine self-administration, responding was well maintained by injections of 30-300 microgram/kg of nicotine. Nicotine-maintained responding could be reduced by presession treatment with the nicotine antagonist, mecamylamine, or by substitution of saline for nicotine. In a second experiment, responding was maintained under a two-component fixed-ratio schedule of food presentation in which responses during one component (punishment component) also resulted in injections of 10-30 microgram/kg of nicotine. Nicotine markedly suppressed responding during the punishment component but not during the alternating nonpunishment components. The suppressant effects of nicotine could be reversed by presession treatment with either mecamylamine or the antianxiety drug chlordiazepoxide, or by substitution of saline for nicotine. Nicotine had pronounced effects both as a reinforcer and as a punisher; the nature of the effects depended on the schedule under which nicotine was administered. PMID:7060749

  14. [A review of the effects of nicotine on schizophrenia].

    PubMed

    Bidzan, Leszek

    2007-01-01

    It is increasingly appreciated that amongst psychiatric cigarette smokers, those with schizophrenia have elevated rates of smoking compared to the general population. Nicotine seems to improve cognitive functions critically affected in schizophrenia. There is substantial evidence that nicotine could be used by patients with schizophrenia as a "self-medication" to improve deficits in attention, cognition, and information processing. Perhaps nicotine has influence on intensity of side effects of antipsychotic medication. Nicotine treatment modulates both dopaminergic and glutamatergic neurotransmission, and these effects are specific both to brain region and functional system. Understanding how and why schizophrenic individuals use nicotine may lead to the development of new treatments for both schizophrenia and nicotine dependence. PMID:18421928

  15. Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal.

    PubMed

    Watkins, S S; Koob, G F; Markou, A

    2000-02-01

    The neurobiology of nicotine addiction is reviewed within the context of neurobiological and behavioral theories postulated for other drugs of abuse. The roles of various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, gamma-aminobutyric acid, and opioid peptides in acute nicotine reinforcement and withdrawal from chronic administration are examined followed by a discussion of potential neuroadaptations within these neurochemical systems that may lead to the development of nicotine dependence. The link between nicotine administration, depression and schizophrenia are also discussed. Finally, a theoretical model of the neurobiological mechanisms underlying acute nicotine withdrawal and protracted abstinence involves alterations within dopaminergic, serotonergic, and stress systems that are hypothesized to contribute to the negative affective state associated with nicotine abstinence.

  16. Food consumption patterns of Balearic Islands' adolescents depending on their origin.

    PubMed

    Llull, Rosa; Bibiloni, Mar; Pons, Antoni; Tur, Josep A

    2015-04-01

    Over the last decade, the immigrant population of the Balearic Islands archipelago (Spain), in the Mediterranean, has risen to 22% of its total population. The aim of this study was to assess food consumption patterns among Balearic Islands' adolescents depending on their origin. A population-based cross-sectional nutritional survey was carried out in the Balearic Islands (2007-2008; n = 1,231; 12-17 years old). Dietary assessment was based on a 145-item semi-quantitative food-frequency questionnaire. Food consumption differences between the adolescents' point of origin and time of arrival were been studied, as well as average daily meals and snacks. The adolescents' origin and number of years living in the Balearic Islands were also assessed. Native adolescents and immigrants from other Mediterranean countries showed healthier food consumption patterns than their peers from non-Mediterranean countries. Immigrant adolescents adapted their eating patterns to native dietary patterns increasingly, the longer they lived in the Balearic Islands. PMID:25012273

  17. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    SciTech Connect

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  18. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2.

  19. Individuality and contextual influences on drug dependence: a 15-year Prospective longitudinal study of adolescents from Harlem.

    PubMed

    Brook, Judith S; Lee, Jung Yeon; Brown, Elaine N; Finch, Stephen J; Brook, David W

    2012-01-01

    In this 15-year longitudinal study the authors investigated individual and contextual factors that predispose adolescents from a disadvantaged urban area to drug dependence in adulthood. Adolescents were recruited from schools serving East Harlem in New York City. Of the 838 participants followed to adulthood, 59% were women, 55% were African American, and 45% were Puerto Rican. Self-report data were obtained on externalizing and internalizing problems, substance use, and contextual influences across adolescence and young adulthood. Drug dependence was assessed in adulthood. Multivariate logistic regressions of drug dependence were performed on the whole sample and separately by gender. Each of the domains was associated with adult drug dependence. Although mean gender differences were found, most associations of risk factors with drug dependence did not vary significantly by gender. Treating externalizing and internalizing problems, reducing substance use, and providing coping skills for adverse contextual influences in adolescence and young adulthood may reduce the likelihood of becoming drug dependent in adulthood.

  20. Pharmacologic characterization of a nicotine-discriminative stimulus in rhesus monkeys.

    PubMed

    Cunningham, Colin S; Javors, Martin A; McMahon, Lance R

    2012-06-01

    This study examined mechanisms by which nicotine (1.78 mg/kg base s.c.) produces discriminative stimulus effects in rhesus monkeys. In addition to nicotine, various test compounds were studied including other nicotinic acetylcholine receptor agonists (varenicline and cytisine), antagonists [mecamylamine and the α4β2 receptor-selective antagonist dihydro-β-erythroidine (DHβE)], a nicotinic acetylcholine receptor antagonist/indirect-acting catecholamine agonist (bupropion), and non-nicotinics (cocaine and midazolam). Nicotine, varenicline, and cytisine dose-dependently increased drug-lever responding; the ED(50) values were 0.47, 0.53, and 39 mg/kg, respectively. Bupropion and cocaine produced 100% nicotine-lever responding in a subset of monkeys, whereas mecamylamine, DHβE, and midazolam produced predominantly vehicle-lever responding. The training dose of nicotine resulted in 1128 ng/ml cotinine in saliva. Mecamylamine antagonized the discriminative stimulus effects of nicotine and varenicline, whereas DHβE was much less effective. Nicotine and varenicline had synergistic discriminative stimulus effects. In monkeys responding predominantly on the vehicle lever after a test compound (bupropion, cocaine, and midazolam), that test compound blocked the nicotine-discriminative stimulus, perhaps reflecting a perceptual-masking phenomenon. These results show that nicotine, varenicline, and cytisine produce discriminative stimulus effects through mecamylamine-sensitive receptors (i.e., nicotinic acetylcholine) in primates, whereas the involvement of DHβE-sensitive receptors (i.e., α4β2) is unclear. The current nicotine-discrimination assay did not detect a difference in agonist efficacy between nicotine, varenicline, and cytisine, but did show evidence of involvement of dopamine. The control that nicotine has over choice behavior can be disrupted by non-nicotinic compounds, suggesting that non-nicotinics could be exploited to decrease the control that tobacco has

  1. Inside-out neuropharmacology of nicotinic drugs.

    PubMed

    Henderson, Brandon J; Lester, Henry A

    2015-09-01

    Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25660637

  2. Nicotine and lung development.

    PubMed

    Maritz, Gert S

    2008-03-01

    Nicotine is found in tobacco smoke. It is a habit forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the antioxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule, thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastically increased cAMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mother's milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals that were exposed to nicotine via the placenta and mother's milk, and thus during phases of lung development characterized by rapid cell division, is likely due to "programming" induced by nicotine. It is, therefore, not advisable to use nicotine during gestation and lactation. PMID:18383131

  3. A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

    ERIC Educational Resources Information Center

    Patten, Christi A.

    2000-01-01

    Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

  4. The roles of familial alcoholism and adolescent family harmony in young adults' substance dependence disorders: mediated and moderated relations.

    PubMed

    Zhou, Qing; King, Kevin M; Chassin, Laurie

    2006-05-01

    This study examined the prospective relations among family history density of alcoholism (FHD), adolescent family harmony, and young adults' alcohol and drug dependence. Family harmony was rated by mothers and fathers in adolescence, and young adults' substance dependence diagnoses were obtained through structured interviews. Higher FHD predicted lower adolescent family harmony, which in turn increased young adults' odds of being diagnosed with drug dependence (with and without alcohol dependence) compared to no diagnoses or to alcohol dependence only. Family harmony also interacted with FHD such that the protective effect of family harmony on young adults' drug dependence with or without alcohol dependence decreased as FHD rose, and was nonsignificant at high levels of FHD. The findings suggest the importance of distinguishing among alcohol and drug dependence disorders and examining their differential etiological pathways, and also suggest that the protective effects of harmonious family environments on substance dependence may be limited at high levels of FHD.

  5. Biodegradation of nicotine by a newly isolated Pseudomonas stutzeri JZD

    NASA Astrophysics Data System (ADS)

    Petricevic, Jelena; Gujanicic, Vera; Radic, Danka; Jovicic Petrovic, Jelena; Jovic, Jelena; Raicevic, Vera

    2013-04-01

    The tobacco-manufacturing process and all activities that use tobacco, produce solid or liquid wastes with high concentrations of nicotine. Nicotine is a significant toxic waste product in tobacco industry. This waste is classified as 'toxic and hazardous' by European Union regulations when the nicotine content exceeds 500 milligrams per kilogram dry weight. Therefore, there is a major environmental requirement to remove nicotine from tobacco wastes. Bioremediation techniques which involve nicotine degradation by microorganisms have attracted attention during the last years, because microorganisms have the potential to reduce nicotine levels in tobacco and to detoxify tobacco wastes. The aim of this study is isolation and identification of nicotine degraded bacteria and optimization of nicotine degradation in laboratory conditions. An aerobic bacterial strain capable of effectively degrading nicotine was isolated from the tobacco industry waste, Serbia. After isolation, the liquid culture was spread onto the solid plates of the nicotine inorganic salt medium using the dilution plate method. Cell morphology of strain was observed by a light microscope and physiological characteristics were determined by Api technique and sequence analyzes of 16S rDNA. This isolate was identified as Pseudomonas stutzeri based on morphology, physiological characteristics, and Apiweb technique. Comparison with sequences available in data library showed the 99% similarity with 16S rDNA gene sequence of the species Pseudomonas stutzeri ( GenBank Acc. No. CP003725). We analyzed the effect of initial nicotine concentration (1g/L, 1.5 g/L, 2.5 g/L) on microbial activity in aim to optimize biodegradation. The effect of cultivation temperature (25°C; 30°C; 37°C) on nicotine degradation by P. stutzeri was evaluated after 24 h of cultivation, with 1.5 g/L nicotine added as the sole carbon source. Effect of biodegradation has depended on initial concentration. During incubation, number of

  6. Individuality and Contextual Influences on Drug Dependence: A 15-Year Prospective Longitudinal Study of Adolescents from Harlem

    ERIC Educational Resources Information Center

    Brook, Judith S.; Lee, Jung Yeon; Brown, Elaine N.; Finch, Stephen J.; Brook, David W.

    2012-01-01

    In this 15-year longitudinal study the authors investigated individual and contextual factors that predispose adolescents from a disadvantaged urban area to drug dependence in adulthood. Adolescents were recruited from schools serving East Harlem in New York City. Of the 838 participants followed to adulthood, 59% were women, 55% were African…

  7. Dopaminergic signaling mediates the motivational response underlying the opponent process to chronic but not acute nicotine.

    PubMed

    Grieder, Taryn E; Sellings, Laurie H; Vargas-Perez, Hector; Ting-A-Kee, Ryan; Siu, Eric C; Tyndale, Rachel F; van der Kooy, Derek

    2010-03-01

    The mesolimbic dopamine (DA) system is implicated in the processing of the positive reinforcing effect of all drugs of abuse, including nicotine. It has been suggested that the dopaminergic system is also involved in the aversive motivational response to drug withdrawal, particularly for opiates, however, the role for dopaminergic signaling in the processing of the negative motivational properties of nicotine withdrawal is largely unknown. We hypothesized that signaling at dopaminergic receptors mediates chronic nicotine withdrawal aversions and that dopaminergic signaling would differentially mediate acute vs dependent nicotine motivation. We report that nicotine-dependent rats and mice showed conditioned place aversions to an environment paired with abstinence from chronic nicotine that were blocked by the DA receptor antagonist alpha-flupenthixol (alpha-flu) and in DA D(2) receptor knockout mice. Conversely, alpha-flu pretreatment had no effect on preferences for an environment paired with abstinence from acute nicotine. Taken together, these results suggest that dopaminergic signaling is necessary for the opponent motivational response to nicotine in dependent, but not non-dependent, rodents. Further, signaling at the DA D(2) receptor is critical in mediating withdrawal aversions in nicotine-dependent animals. We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals.

  8. Dopaminergic signaling mediates the motivational response underlying the opponent process to chronic but not acute nicotine.

    PubMed

    Grieder, Taryn E; Sellings, Laurie H; Vargas-Perez, Hector; Ting-A-Kee, Ryan; Siu, Eric C; Tyndale, Rachel F; van der Kooy, Derek

    2010-03-01

    The mesolimbic dopamine (DA) system is implicated in the processing of the positive reinforcing effect of all drugs of abuse, including nicotine. It has been suggested that the dopaminergic system is also involved in the aversive motivational response to drug withdrawal, particularly for opiates, however, the role for dopaminergic signaling in the processing of the negative motivational properties of nicotine withdrawal is largely unknown. We hypothesized that signaling at dopaminergic receptors mediates chronic nicotine withdrawal aversions and that dopaminergic signaling would differentially mediate acute vs dependent nicotine motivation. We report that nicotine-dependent rats and mice showed conditioned place aversions to an environment paired with abstinence from chronic nicotine that were blocked by the DA receptor antagonist alpha-flupenthixol (alpha-flu) and in DA D(2) receptor knockout mice. Conversely, alpha-flu pretreatment had no effect on preferences for an environment paired with abstinence from acute nicotine. Taken together, these results suggest that dopaminergic signaling is necessary for the opponent motivational response to nicotine in dependent, but not non-dependent, rodents. Further, signaling at the DA D(2) receptor is critical in mediating withdrawal aversions in nicotine-dependent animals. We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals. PMID:20032966

  9. Nicotine withdrawal: a behavioral assessment using schedule controlled responding, locomotor activity, and sensorimotor reactivity.

    PubMed

    Helton, D R; Modlin, D L; Tizzano, J P; Rasmussen, K

    1993-01-01

    Three different behavioral measures were used to assess the effects of abrupt cessation of chronic nicotine treatment. Nicotine (0, 3, or 6 mg/kg per day) was continuously administered for 12 days in rats by surgically implanting Alzet osmotic mini-pumps subcutaneously. Experiment 1 employed a light/dark discrimination task. There were no significant effects on number of responses or percent correct responding either during nicotine administration, or following cessation of nicotine. Experiment 2 examined ambulatory (locomotor) and nonambulatory activity. Chronic nicotine administration produced significant dose-dependent increases in both ambulatory and nonambulatory activity during the first 3 days of exposure. However, no significant alterations were seen in activity levels following nicotine cessation. Experiment 3 examined sensorimotor reactivity using the auditory startle response. During nicotine withdrawal, significant increases were seen in startle amplitude in both nicotine groups for 4 days. Nicotine (0.4 mg/kg, IP) administered before startle testing during the withdrawal phase attenuated the increased reactivity seen during nicotine cessation. These studies indicate that 1) rats display increased sensorimotor reactivity after cessation of chronic nicotine exposure, and 2) the expression of nicotine dependence and withdrawal is dependent on the behavioral task employed. PMID:7855182

  10. In vitro study of nicotine release from smokeless tobacco.

    PubMed

    Nasr, M M; Reepmeyer, J C; Tang, Y

    1998-01-01

    Four brands (Copenhagen Snuff, Skoal Bandit Classic, Skoal Wintergreen Long Cut, and Skoal Wintergreen Fine Cut) of smokeless tobacco products were tested for their rate of nicotine release into artificial saliva via direct contact or through a dialysis bag. Nicotine was determined by reversed-phase liquid chromatography. When samples were in direct contact with artificial saliva, most of the nicotine was released from the tobacco in the first minute. Nicotine release from Skoal Bandit Classic, marketed as smokeless tobacco in a sachet, was slower with the sachet intact than without the sachet. When smokeless tobacco and artificial saliva were placed inside a dialysis bag, nicotine release was much slower and primarily depended upon the permeability of the dialysis membrane. Although total nicotine was lowest for Skoal Bandit Classic, little difference was seen in nicotine release rates among the brands tested. When smokeless tobacco was placed in dialysis bags with artificial saliva outside, a significant difference was seen in rates of nicotine migration through the membrane. In this model, nicotine release from Copenhagen Snuff was much faster than from Skoal Bandit Classic with or without the sachet. This difference may be related to the pH of the smokeless tobacco products.

  11. Sensory reinforcement-enhancing effects of nicotine via smoking.

    PubMed

    Perkins, Kenneth A; Karelitz, Joshua L

    2014-12-01

    As has been found in nicotine research on animals, research on humans has shown that acute nicotine enhances reinforcement from rewards unrelated to nicotine intake, but this effect may be specific to rewards from stimuli that are "sensory" in nature. We assessed acute effects of nicotine via smoking on responding for music or video rewards (sensory), for monetary reward (nonsensory), or for no reward (control), to gauge the generalizability of nicotine's reinforcement-enhancing effects. Using a fully within-subjects design, dependent smokers (N = 20) participated in 3 similar experimental sessions, each following overnight abstinence (verified by carbon monoxide <10 ppm) and varying only in the smoking condition. Sessions involved no smoking or smoking "denicotinized" ("denic;" 0.05 mg) or nicotine (0.6 mg) Quest brand cigarettes in controlled fashion prior to responding on a simple operant computer task for each reward separately using a progressive ratio schedule. The reinforcing effects of music and video rewards, but not money, were significantly greater due to the nicotine versus denic cigarette (i.e., nicotine per se), whereas there were no differences between denic cigarette smoking and no smoking (i.e., smoking behavior per se), except for no reward. These effects were not influenced by withdrawal relief from either cigarette. Results that generalize from an auditory to a visual reward confirm that acute nicotine intake per se enhances the reinforcing value of sensory rewards, but its effects on the value of other (perhaps nonsensory) types of rewards may be more modest.

  12. Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour.

    PubMed

    Llorente-Berzal, Alvaro; Fuentes, Sílvia; Gagliano, Humberto; López-Gallardo, Meritxell; Armario, Antonio; Viveros, María-Paz; Nadal, Roser

    2011-10-01

    Early life experiences such as maternal deprivation (MD) exert long-lasting changes in adult behaviour and reactivity to stressors. Adolescent exposure to cannabinoids is a predisposing factor in developing certain psychiatric disorders. Therefore, the combination of the two factors could exacerbate the negative consequences of each factor when evaluated at adulthood. The objective of this study was to investigate the long-term effects of early MD [24 hours at postnatal day (PND) 9] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (0.4 mg/kg, PND 28-42) on diverse behavioural and physiological responses of adult male and female Wistar rats. We tested them in the prepulse inhibition (PPI) of the startle response and analysed their exploratory activity (holeboard) and anxiety (elevated plus maze, EPM). In addition, we evaluated their adrenocortical reactivity in response to stress and plasma leptin levels. Maternal behaviour was measured before and after deprivation. MD induced a transient increase of maternal behaviour on reuniting. In adulthood, maternally deprived males showed anxiolytic-like behaviour (or increased risk-taking behaviour) in the EPM. Adolescent exposure to the cannabinoid agonist induced an impairment of the PPI in females and increased adrenocortical responsiveness to the PPI test in males. Both, MD and adolescent cannabinoid exposure also induced sex-dependent changes in plasma leptin levels and body weights. The present results indicate that early MD and adolescent cannabinoid exposure exerted distinct sex-dependent long-term behavioural and physiological modifications that could predispose to the development of certain neuropsychiatric disorders, though no synergistic effects were found.

  13. Cannabis receptor haplotype associated with fewer cannabis dependence symptoms in adolescents.

    PubMed

    Hopfer, Christian J; Young, Susan E; Purcell, Shaun; Crowley, Thomas J; Stallings, Michael C; Corley, Robin P; Rhee, Soo Hyun; Smolen, Andrew; Krauter, Ken; Hewitt, John K; Ehringer, Marissa A

    2006-12-01

    Cannabis is a major substance of abuse, and the gene encoding for the central cannabinoid receptor (CNR1) is a logical candidate gene for vulnerability toward developing symptoms of cannabis dependence. We studied four single-nucleotide polymorphisms (SNPs) in the CNR1 gene for association with having one or more symptoms of cannabis dependence in 541 adolescent subjects who had all tried cannabis five or more times. Cases (327) were defined as those who had tried marijuana and developed one or more symptoms, and controls (214) as those who had tried marijuana but developed no dependence symptoms. Cannabis dependence symptoms were assessed in these youth when they were 17 or older with the Composite International Diagnostic Interview--Substance Abuse Module. Univariate (single-marker) association tests demonstrated that SNP rs806380, located in intron 2 of the CNR1 gene, was significantly associated with developing one or more cannabis dependence symptoms, with the G allele having a protective effect (P < 0.02). This was consistent with the results of the global haplotype test (P < 0.01). One of the common haplotypes examined (present in 21% of the subjects) was significantly associated with a lower rate of having one or more cannabis dependence symptoms. Our findings provide evidence suggesting that a common CNR1 haplotype is associated with developing fewer cannabis dependence symptoms among adolescents who have experimented with cannabis.

  14. Boys do it the right way: sex-dependent amygdala lateralization during face processing in adolescents.

    PubMed

    Schneider, S; Peters, J; Bromberg, U; Brassen, S; Menz, M M; Miedl, S F; Loth, E; Banaschewski, T; Barbot, A; Barker, G; Conrod, P J; Dalley, J W; Flor, H; Gallinat, J; Garavan, H; Heinz, A; Itterman, B; Mallik, C; Mann, K; Artiges, Eric; Paus, T; Poline, J-B; Rietschel, M; Reed, L; Smolka, M N; Spanagel, R; Speiser, C; Ströhle, A; Struve, M; Schumann, G; Büchel, C

    2011-06-01

    Previous studies have observed a sex-dependent lateralization of amygdala activation related to emotional memory. Specifically, it was shown that the activity of the right amygdala correlates significantly stronger with memory for images judged as arousing in men than in women, and that there is a significantly stronger relationship in women than in men between activity of the left amygdala and memory for arousing images. Using a large sample of 235 male adolescents and 235 females matched for age and handedness, we investigated the sex-specific lateralization of amygdala activation during an emotional face perception fMRI task. Performing a formal sex by hemisphere analysis, we observed in males a significantly stronger right amygdala activation as compared to females. Our results indicate that adolescents display a sex-dependent lateralization of amygdala activation that is also present in basic processes of emotional perception. This finding suggests a sex-dependent development of human emotion processing and may further implicate possible etiological pathways for mental disorders most frequent in adolescent males (i.e., conduct disorder).

  15. Cortical and subcortical volumes in adolescents with alcohol dependence but without substance or psychiatric comorbidities

    PubMed Central

    Fein, George; Greenstein, David; Cardenas, Valerie A.; Cuzen, Natalie L.; Foucheb, Jean-Paul; Ferrett, Helen; Thomas, Keven; Stein, Dan J.

    2013-01-01

    Most prior studies of the effects of excessive alcohol intake on the adolescent brain examined alcohol use dependent samples with comorbid psychiatric and substance use disorders. In the Cape Town region, we identified a sizeable cohort of adolescents with alcohol use disorders (AUD) without externalizing or other psychiatric disorders. We examined brain morphology in 64 such adolescents compared to age and gender matched healthy controls. Magnetic resonance imaging data were analyzed using FSL’s FIRST software for subcortical volumes, and cortical gray matter (GM) was analyzed using voxel based morphometry (VBM) and regions of interest (ROI) analysis. AUD boys had smaller thalamic and putamen volumes compared to non-drinking boys, while AUD girls had larger thalamic and putamen volumes compared to non-drinking girls. VBM revealed a large region of decreased GM density in AUDs compared to controls located in the left lateral frontal, temporal, and parietal lobes, extending medially deep into the parietal lobe. Smaller GM volume in this region was also present when examined using ROI analysis. Our lack of findings in other brain regions, particularly hippocampus, suggests that reports of smaller brain volumes in adolescent AUDs in the literature are a consequence of psychiatric and substance abuse comorbidities. PMID:23916536

  16. Variation in the α 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content.

    PubMed

    Macqueen, D A; Heckman, B W; Blank, M D; Janse Van Rensburg, K; Park, J Y; Drobes, D J; Evans, D E

    2014-02-01

    A single-nucleotide polymorphism (SNP) in the α5 nicotinic acetylcholine receptor subunit gene, rs16969968, has been repeatedly associated with both smoking and respiratory health phenotypes. However, there remains considerable debate as to whether associations with lung cancer are mediated through effects on smoking behavior. Preclinical studies suggest that α5 receptor subunit expression and function may have a direct role in nicotine titration during self administration. The present study investigated the association of CHRNA5 polymorphisms and smoking topography in 66 smokers asked to smoke four nicotine-containing (nicotine yield=0.60 mg) and four placebo (nicotine yield <0.05 mg) cigarettes, during separate experimental sessions. Genotype at rs16969968 predicted nicotine titration, with homozygotes for the major allele (G:G) displaying significantly reduced puff volume in response to nicotine, whereas minor allele carriers (A:G or A:A) produced equivalent puff volumes for placebo and nicotine cigarettes. The present results suggest that puff volume may be a more powerful objective phenotype of smoking behavior than self-reported cigarettes per day and nicotine dependence. Further, these results suggest that the association between rs16969968 and lung cancer may be mediated by the quantity of smoke inhaled.

  17. Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications.

    PubMed

    D'Souza, Manoranjan S

    2016-01-01

    Morbidity and mortality associated with tobacco smoking constitutes a significant burden on healthcare budgets all over the world. Therefore, promoting smoking cessation is an important goal of health professionals and policy makers throughout the world. Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco. A majority of the currently available FDA-approved smoking cessation medications act via neuronal nicotinic receptors. These medications are effective in approximately half of all the smokers, who want to quit and relapse among abstinent smokers continues to be high. In addition to relapse among abstinent smokers, unpleasant effects associated with nicotine withdrawal are a major motivational factor in continued tobacco smoking. Over the last two decades, animal studies have helped in identifying several neural substrates that are involved in nicotine-dependent behaviors including those associated with nicotine withdrawal and relapse to tobacco smoking. In this review, first the role of specific brain regions/circuits that are involved in nicotine dependence will be discussed. Next, the review will describe the role of specific nicotinic receptor subunits in nicotine dependence. Finally, the review will discuss the role of classical neurotransmitters (dopamine, serotonin, noradrenaline, glutamate, and γ-aminobutyric acid) as well as endogenous opioid and endocannabinoid signaling in nicotine dependence. The nicotinic and nonnicotinic neural substrates involved in nicotine-dependent behaviors can serve as possible targets for future smoking cessation medications.

  18. Relationships Between Marijuana Dependence and Condom Use Intentions and Behavior Among Justice-Involved Adolescents

    PubMed Central

    Caldwell Hooper, Ann E.; Thayer, Rachel E.; Magnan, Renee E.; Bryan, Angela D.

    2013-01-01

    The current study examined the relationships among marijuana dependence, a theoretical model of condom use intentions, and subsequent condom use behavior in justice-involved adolescents. Participants completed baseline measures of prior sexual and substance use behavior. Of the original 720 participants, 649 (90.13 %) completed follow-up measures 6 months later. There were high levels of marijuana use (58.7 % met criteria for dependence) and risky sexual behavior among participants. Baseline model constructs were associated with condom use intentions, and intentions were a significant predictor of condom use at follow-up. Marijuana dependence did not significantly influence the relationships between model constructs, nor did it moderate the relationship of model constructs with subsequent condom use. Findings suggest that the theoretical model of condom use intentions is equally valid regardless of marijuana dependence status, suggesting that interventions to reduce sexual risk behavior among both marijuana dependent and non-dependent justice-involved adolescents can be appropriately based on the model. PMID:23370834

  19. Alcohol, nicotine, caffeine, and mental disorders

    PubMed Central

    Crocq, Marc-Antoine

    2003-01-01

    Alcohol, nicotine, and caffeine are the most widely consumed psychotropic drugs worldwide. They are largely consumed by normal individuals, but their use is even more frequent in psychiatric patients, Thus, patients with schizophrenia tend to abuse all three substances. The interrelationships between depression and alcohol are complex. These drugs can all create dependence, as understood in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Alcohol abuse is clearly deleterious to the brain, provoking acute and chronic mental disorders, ranging from intoxication with impairment of cognition, to delirium tremens, halluosis, and dementia. In contrast, the main health consequences of nicotine, notably cancer and cardiovascular disases, lie outside the realm of psychiatry However, the mes of nicotine dependence and motivation to smoke or quit are of concern to psychiatrists. PMID:22033899

  20. Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina.

    PubMed

    Bach, Daniel J; Tenaglia, Matthew; Baker, Debra L; Deats, Sean; Montgomery, Erica; Pagán, Oné R

    2016-10-01

    Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine's beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions. PMID:27616704

  1. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    SciTech Connect

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

    2014-10-15

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

  2. Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina.

    PubMed

    Bach, Daniel J; Tenaglia, Matthew; Baker, Debra L; Deats, Sean; Montgomery, Erica; Pagán, Oné R

    2016-10-01

    Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine's beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions.

  3. Damsels in distress: dependency themes in fiction for children and adolescents.

    PubMed

    White, H

    1986-01-01

    In a study of dependency themes in 113 recently published fictional books for children and adolescents, females and males were compared in situations where one character helped or influenced another. Regardless of the context in which help was given, and regardless of whether it was of an active or passive nature, females were more likely to receive than to give help, and males were more likely to give than to receive help. Males were even more likely to provide emotional support or encouragement, a stereotypically female virtue. The cultural stereotype of the dependent female, however, was reflected in the girl and women characters. PMID:3739822

  4. Damsels in distress: dependency themes in fiction for children and adolescents.

    PubMed

    White, H

    1986-01-01

    In a study of dependency themes in 113 recently published fictional books for children and adolescents, females and males were compared in situations where one character helped or influenced another. Regardless of the context in which help was given, and regardless of whether it was of an active or passive nature, females were more likely to receive than to give help, and males were more likely to give than to receive help. Males were even more likely to provide emotional support or encouragement, a stereotypically female virtue. The cultural stereotype of the dependent female, however, was reflected in the girl and women characters.

  5. Adolescent Use of Electronic Cigarettes: An Emergent Health Concern for Pediatric Nurses.

    PubMed

    Johnson, Molly; Pennington, Nicole

    2015-01-01

    Recent statistics show an increasing trend of electronic cigarette usage among adolescents. Despite common misconceptions, electronic cigarette use does not reduce cigarette use among adolescents and can potentially increase cigarette dependence via nicotine addiction and modeling of smoking behaviors. Pediatric nurses and health care providers should be aware of the popularity and safety concerns of electronic cigarettes so that they can properly provide education regarding the possible negative health effects of adolescent electronic cigarette use, raise awareness of this public health concern, and impact policies in their communities.

  6. Sabotaging siblings: an overlooked aspect of family therapy with drug dependent adolescents.

    PubMed

    Huberty, D J; Huberty, C E

    1986-01-01

    Successful family therapy for drug dependence on the part of an adolescent must include sensitivity to the roles that other siblings play in the family system. Therapists must be aware of the possible infectiousness of substance abuse from an older sibling to a younger sibling. The sabotaging positions and roles that siblings play in relationship to the drug abuser must receive the kind of attention in family therapy that allows a loosening of these roles. What too often happens is a tightening of the grip on these positions when the drug dependent adolescent is identified as the patient, client or the one with the problems as well as the one who is responsible for the family's pain. Without an emphasis on confronting needed changes by others in the sibling subsystem, the recovering adolescent will experience a deep discouragement from a lack of genuine support from brothers and sisters. Feelings of failure and inferiority will point in the direction of rejection and a likely return to an identity as sick, bad and delinquent. Sabotaging siblings understandably fear changes in the familiar family positions and functions. However, in order for these brothers and sisters to welcome the former scapegoat back home, they must make room for the returning member, not as a drug abuser but as a person. They must allow him/her to find a new role of achievement, success identity and inclusion within the total family system, and provide acceptance as a truly valued sibling.

  7. Association Between Depressive Symptoms and Negative Dependent Life Events from Late Childhood to Adolescence

    PubMed Central

    Johnson, Daniel P.; Whisman, Mark A.; Corley, Robin P.; Hewitt, John K.; Rhee, Soo Hyun

    2012-01-01

    The association between stressful life events and depression has been consistently supported in the literature; however, studies of the developmental trajectories of these constructs and the nature of their association over time are limited. We examined trajectories of depressive symptoms and negative dependent life events and the associations between these constructs in a sample of 916 youth assessed annually from age 9 to 16, using latent growth curve modeling. Youth depressive symptoms, as rated by youth, parents, and teachers, decreased from late childhood into adolescence, whereas rates of youth-rated life events did not change significantly over time. Initial levels of depressive symptoms were positively associated with initial levels of life events. Furthermore, after controlling for the initial association between the two constructs, increases in depressive symptoms (as assessed by parents and youth) were positively associated with increases in life events over time. The study builds on prior research by focusing specifically on negative dependent life events, examining results across multiple informants, and employing latent growth curve modeling to evaluate associations between trajectories of life events and depressive symptoms in a longitudinal adolescent sample. Additional studies employing latent growth modeling to examine the changes in this association during adolescence are needed. PMID:22592931

  8. The development of socio-motivational dependency from early to middle adolescence

    PubMed Central

    Jagenow, Danilo; Raufelder, Diana; Eid, Michael

    2015-01-01

    Research on students’ motivation has shown that motivation can be enhanced or undermined by social factors. However, when interpreting such findings, interindividual differences, and intraindividual changes underlying students’ perception of peers and teachers as a source of motivation are often neglected. The aim of the present study was to complement our understanding of socio-motivational dependency by investigating differences in the development of students’ socio-motivational dependency from early to middle adolescence. Data from 1088 students on their perceptions of peers and teachers as positive motivators when students were in seventh and eighth grade were compared with data of the same sample 2 years later. Latent class analysis supported four different motivation types (MT): (1) teacher-dependent MT, (2) peer-dependent MT, (3) teacher-and-peer-dependent MT, and (4) teacher-and-peer-independent MT. Latent transition analysis revealed substantial changes between the groups. The perceived teacher influence on students’ academic motivation increased from early to middle adolescence. Divergent roles of peers and teachers on students’ academic motivation are discussed. PMID:25762966

  9. Nicotine Nasal Spray

    MedlinePlus

    ... program, which may include support groups, counseling, or specific behavior change techniques. Nicotine nasal spray is in ... bottles at room temperature and away from excess heat and moisture (not in the bathroom). Discard used ...

  10. Nicotine and tobacco

    MedlinePlus

    ... ease your withdrawal symptoms. Health experts warn that e-cigarettes are not a replacement therapy for cigarette smoking. ... not known exactly how much nicotine is in e-cigarette cartridges, because information on labels is often wrong. ...

  11. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    PubMed

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.

  12. Assessing adolescents with insulin-dependent diabetes mellitus: a multiple perspective pilot study using visual illness narratives and interviews.

    PubMed

    Buchbinder, Mara H; Detzer, Mark J; Welsch, Robert L; Christiano, Ann S; Patashnick, Jennifer L; Rich, Michael

    2005-01-01

    This study explored the illness experiences of adolescents with insulin-dependent diabetes mellitus (IDDM) using Video Intervention/Prevention Assessment (VIA). Five adolescents with IDDM were asked to videotape 8 hours of their lives over a 1-month period. At the conclusion of the study, the primary investigator interviewed each adolescent and their diabetes clinician. VIA visual illness narratives and follow-up interviews provided clinically important, previously unknown information about how adolescents live with diabetes, including the negative and positive influences of diabetes on the family unit and the individual, that parental involvement was associated with adolescents' diabetes control, and that gender may be a significant mediating factor in control. PMID:15661602

  13. Inside-out neuropharmacology of nicotinic drugs

    PubMed Central

    Henderson, Brandon J.; Lester, Henry A.

    2015-01-01

    Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as “inside-out pharmacology”. This term contrasts with the better-known, acute, “outside-in” effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. PMID:25660637

  14. Historical and Current Perspective on Tobacco use and Nicotine Addiction

    PubMed Central

    Dani, John A.; Balfour, David J.K.

    2011-01-01

    Although the addictive influence of tobacco was recognized very early, the modern concepts of nicotine addiction have relied on knowledge of cholinergic neurotransmission and nicotinic acetylcholine receptors (nAChRs). The discovery of the “receptive substance” by Langley, that would turn out to be nAChRs, and “Vagusstoff” (acetylcholine) by Loewi, coincided with an exciting time when the concept of chemical synaptic transmission was being formulated. More recently, the application of more powerful techniques and the study of animal models that replicate key features of nicotine dependence have led to important advancements in our understanding of molecular, cellular, and systems mechanisms of nicotine addiction. In this Review, we present a historical perspective and overview of the research that has led to our present understanding of nicotine addiction. PMID:21696833

  15. Involvement of the rostral agranular insular cortex in nicotine self-administration in rats.

    PubMed

    Pushparaj, Abhiram; Kim, Aaron S; Musiol, Martin; Trigo, Jose M; Le Foll, Bernard

    2015-09-01

    Our prior work demonstrated the involvement of the caudal granular subregion of the insular cortex in a rat model of nicotine self-administration. Recent studies in various animal models of addiction for nicotine and other drugs have identified a role for the rostral agranular subregion (RAIC). The current research was undertaken to examine the involvement of the RAIC in a rat model of nicotine self-administration. We investigated the inactivating effects of local infusions of a γ-aminobutyric acid agonist mixture (baclofen/muscimol) into the RAIC on nicotine self-administration under a fixed-ratio 5 (FR-5) schedule and on reinstatement of nicotine seeking induced by nicotine-associated cues in rats. We also evaluated the effects of RAIC inactivation on food self-administration under an FR5 schedule as a control. Inactivation of the RAIC decreased nicotine, but not food, self-administration. RAIC inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues. Our study indicates that the RAIC is involved in nicotine-taking and nicotine-seeking in rats. Modulating insular cortex function appears to be a promising approach for nicotine dependence treatment.

  16. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells.

    PubMed

    Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

    2016-02-01

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  17. Pathophysiological effects of nicotine on the pancreas: an update.

    PubMed

    Chowdhury, Parimal; MacLeod, Stewart; Udupa, Kodetthor B; Rayford, Phillip L

    2002-07-01

    Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic diseases. It is well recognized that nicotine, a major component in cigarette smoke, is an addictive agent and, therefore, reinforces smoking behavior. The current review update focuses on the genetics of nicotine dependence and its role on the development of pancreatic diseases. The role of smoking and nicotine in pancreatitis and pancreatic cancer development is also discussed. Exposure of laboratory animals to nicotine clearly supports the notion that nicotine can induce pancreatic injury. The mechanism by which nicotine induces such effects is perhaps mediated via signal transduction pathways in the pancreatic acinar cell, leading to enhanced levels of intracellular calcium release, resulting in cytotoxicity and eventual cell death. The induction of pancreatic injury by nicotine may also involve activation and expression of protooncogene, H-ras, which can increase cytosolic calcium via second messenger pathways. Development of pancreatic carcinoma in cigarette smokers as observed in human populations may be the result of activation and mutation of the H-ras gene. A possible pathogenetic mechanism of nicotine in the pancreas activating multiple signal transduction pathways is schematically summarized in Figure 1.

  18. Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FK506 binding protein 5 gene (FKBP5).

    PubMed

    Handley, Elizabeth D; Rogosch, Fred A; Cicchetti, Dante

    2015-11-01

    The current study examined the prospective association between child maltreatment and the development of substance use disorder in adolescence with the aim of investigating pathways underlying this relation, as well as genetic moderation of these developmental mechanisms. Specifically, we tested whether youth who experienced maltreatment prior to age 8 were at risk for the development of marijuana