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Sample records for adolescent nicotine dependence

  1. Nicotine dependence and problem behaviors among urban South African adolescents.

    PubMed

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

    2010-04-01

    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. 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

  3. 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…

  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. 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…

  7. An assessment of nicotine dependence among pregnant adolescents.

    PubMed

    Albrecht, S A; Cornelius, M D; Braxter, B; Reynolds, M D; Stone, C; Cassidy, B

    1999-06-01

    Studies have reported that between 28 and 62% of pregnant teenagers smoke (Cornelius, Taylor, Geva, & Day, 1995; Trollestrup, Frost, & Starzyk, 1992). Because smoking is prevalent among pregnant teenagers, the purpose of this research is to assess nicotine dependence in this high-risk group. This study analyzed baseline data from a sample of pregnant teen smokers who had volunteered to participate in a smoking cessation study (N = 94). Nicotine dependence was measured by adapting the Fagerstrom Tolerance Questionnaire (FTQ; Prokhorov, Pallonen, Fava, Ding, & Niaura, 1996), and by a 6-item withdrawal symptom scale. The overall FTQ score found among pregnant adolescents was 3.10 (SD = 2.3) compared to the mean overall FTQ score among vocational-technical students of 4.27 (SD = 2.2) (Prokhorov et al., 1996). Duration of smoking in years was significantly correlated with the overall FTQ score (r = 0.43, p < .01). Quantity of smoking, as measured by average number of cigarettes smoked, significantly correlated with overall FTQ scores (r = 0.67, p < .01). Lighter smokers were more likely to have previously attempted to quit, however, among the quit attempters, those who smoked 10+ cigarettes per day reported greater severity of withdrawal symptoms than those who smoked less per day. Prenatal education and smoking cessation programs for pregnant teenagers, and pregnant women in general, need to consider that nicotine dependence is an important issue. Early pregnancy may be an opportune time to intervene among pregnant smokers; incentives may be necessary to attract those women who are the heaviest smokers, and possibly the most dependent on nicotine. PMID:10349607

  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. Psychosocial factors in adolescent nicotine dependence symptoms: A sample of high school juniors who smoke daily

    PubMed Central

    Bricker, Jonathan B.; Liu, Jingmin; Ramey, Madelaine; Peterson, Arthur V.

    2012-01-01

    Cross-sectionally examined seven theory-guided psychosocial factors associated with nicotine dependence symptoms in a representative self-report survey of 794 Washington State high school junior daily smokers (93% participation). Outcomes were four nicotine dependence symptoms. Results showed that low self-efficacy for quitting smoking and being around adults who smoke were associated with a 3.48 to 10.35 and a 1.47 to 1.77 times higher odds, respectively, of each of the four nicotine dependence symptoms. These results, needing replication in a longitudinal study, suggest that interventions to enhance self-efficacy to quit smoking and counter adult smoking influences might reduce adolescent nicotine dependence. PMID:22409635

  11. 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

  12. Nicotine dependence measures among adolescents with psychiatric disorders: evaluating symptom expression as a function of dependence severity.

    PubMed

    Strong, David R; Brown, Richard A; Ramsey, Susan E; Myers, Mark G

    2003-10-01

    Using methods based in item response theory, we examined a structured interview assessment of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) nicotine dependence and the Modified Fagerström Tolerance Questionnaire (mFTQ) symptoms to explore the expression of particular symptoms as a function of level of nicotine involvement in a sample of 191 adolescents with psychiatric disorders. Despite our attempts to capture a broad range of smokers, 64% of teens were daily smokers and 68% met DSM-IV criteria for nicotine dependence. This paper describes the relative severity of DSM-IV and mFTQ items, as well as each item's ability to discriminate among individuals at various levels of nicotine involvement. Comparisons across measures revealed that the mFTQ was not particularly sensitive to individual variation in DSM-IV symptom counts, suggesting the physiological components were not strongly related to the predominantly cognitive and behavioral components of the DSM-IV nicotine dependence syndrome. However, the mFTQ relative to the DSM-IV consistently showed stronger relationships to the immediate consequences of nicotine deprivation (urge, craving), supporting the conceptualization of the mFTQ as measuring nicotine exposure. These analyses provide us with some preliminary understanding of the severity of particular symptoms and the order in which symptoms are likely to be expressed across levels of nicotine dependence. PMID:14577990

  13. 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

  14. 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. PMID:25257604

  15. Progression of Nicotine Dependence, Mood Level, and Mood Variability in Adolescent Smokers

    PubMed Central

    Piasecki, Thomas M.; Hedeker, Donald; Dierker, Lisa C.; Mermelstein, Robin J.

    2016-01-01

    Mood processes are theorized to play a role in the initiation and progression of smoking behavior. Available work using real-time assessments in samples of young smokers, including several reports from the Social and Emotional Contexts of Adolescent Smoking Patterns (SECASP) study, has indicated that smoking events acutely improve mood and that escalating smoking frequency may stabilize mood. However, prior analyses have not specifically evaluated within-person change in nicotine dependence, which is conceptually distinguishable from frequent smoking and may be associated with unique mood consequences. The current investigation addressed this question using data from 329 adolescent SECASP participants (9th or 10th grade at recruitment) who contributed mood reports via ecological momentary assessment in up to four 1-week bursts over the course of 24 months. Mixed-effects location-scale analyses revealed that within-person increases in scores on the Nicotine Dependence Syndrome Scale were associated with elevations in negative mood level and increased variability of both positive and negative moods. These effects remained when within-person changes in smoking frequency were covaried and were not fully attributable to a subgroup of youth who rapidly escalated their smoking frequency over time. The findings indicate that adolescents tend to show increasing levels of positive mood states, decreasing levels of negative mood, and diminishing mood variability between ages 16 to 18, but progression of nicotine dependence may counteract some of these developmental gains. Emergence of withdrawal symptoms is a likely explanation for the adverse mood effects associated with dependence progression. PMID:26974687

  16. 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

  17. 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

  18. Linking measures of adolescent nicotine dependence to a common latent continuum.

    PubMed

    Strong, David R; Kahler, Christopher W; Colby, Suzanne M; Griesler, Pamela C; Kandel, Denise

    2009-01-01

    Using the theoretical model of nicotine dependence (ND) operationalized within the Diagnostic and Statistical Manual of Mental Disorder, fourth Edition (DSM-IV: American Psychiatric [American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC]) as a frame of reference, we used methods based in item response theory to link alternative instruments assessing adolescent nicotine dependence severity to a common latent continuum. A multi-ethnic cohort of 6th-10th graders selected from the Chicago Public Schools (CPS) completed five household interviews over 2 years. Youth who reported at least some cigarette use in the last 30 days prior to the interviews at waves W3-W5 completed measures of DSM-IV ND, the Modified Fagertrom Tolerance Questionnaire (mFTQ: Prokhorov et al., 1998) and the Nicotine Dependence Syndrome Scale (NDSS: Shiffman et al., 2004), yielding samples of 253, 241, and 296 respondents at W3-W5, respectively. Confirmatory factor analysis supported a primary dimension of ND. Each instrument's items had complementary and stable relationships to ND across multiple waves of assessment. By aligning symptoms along a common latent ND continuum, we evaluated the consistency of symptoms from different instruments that target similar content. Further, these methods allowed for the examination of the DSM-IV as a continuous index of ND, evaluation of the degree of heterogeneity in levels of ND within groups above and below diagnostic thresholds, and the utility of using the pattern or particular DSM-IV symptoms that led to each score in further differentiating levels of ND. Finally, we examined concurrent validity of the ND continuum and levels of current of smoking at each wave of assessment. PMID:18938047

  19. 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

  20. 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. PMID:23684537

  1. Nicotine Exposure during Adolescence Enhances Behavioral Sensitivity to Nicotine during Adulthood in Wistar Rats

    PubMed Central

    Bracken, Amy L.; Chambers, R. Andrew; Berg, Sarah A.; Rodd, Zachary A.; McBride, William J.

    2011-01-01

    Rationale Drug use during adolescence is associated with an increased propensity for drug dependency during adulthood. Therefore, the effects of adolescent exposure to nicotine on adult behavioral responsiveness to nicotine are of particular importance. Objectives The objective of the current study was to determine if adolescent nicotine exposure would enhance behavioral sensitivity and development of sensitization to nicotine during adulthood. Materials and Methods Male Wistar rats were assigned to one of three groups that received subcutaneous (s.c.) injections of nicotine (0, 0.25, or 0.5 mg/kg) in the home cage for 12 consecutive days during adolescence, PD 31–42. Starting on PD 80, distance traveled, rearing, and stereotypy were recorded in locomotor activity chambers each day for 10 days, following s.c. injections of 0, 0.25, or 0.5 mg/kg nicotine. One week later, a final challenge session took place during which rats were injected with 0.5 mg/kg nicotine. Results Rats exposed to nicotine during adolescence displayed a greater locomotor response to a novel environment than saline-treated rats. Adolescent nicotine treatment also resulted in context-independent sensitization to the acute locomotor activating properties of nicotine, including distance traveled and stereotypy, as measured on the first day of adulthood nicotine exposure. Adolescent nicotine-treated rats displayed increased sensitivity to repeated nicotine exposures during adulthood, compared to adolescent saline-treated rats, as measured by distance traveled, rearing, and stereotypic behaviors. Finally, rats treated with nicotine only during adolescence were more sensitive to a final nicotine challenge during adulthood than rats treated with nicotine only previously during adulthood. Conclusions Overall, the results suggest that adolescent nicotine treatment predisposes adult rats to develop increased behavioral sensitivity to chronic nicotine treatment and to be more sensitive to the initial

  2. Pharmacological Intervention of Nicotine Dependence

    PubMed Central

    Jain, Raka; Gupta, Tina

    2013-01-01

    Nicotine dependence is a major cause of mortality and morbidity all over the world. Various medications have been tried to treat nicotine dependence including nicotine replacement therapy, bupropion, and varenicline. A newer venture to nicotine dependence treatment is a nicotine vaccine which is yet to get footsteps in common practice. The present review assimilates various pharmacotherapeutic measures to address nicotine dependence. However, it is to be noted that psychological interventions, when combined with pharmacotherapy, offer the greatest benefits to the patients. PMID:24490153

  3. Nicotine Exposure during Adolescence Leads to Short- and Long-Term Changes in Spike Timing-Dependent Plasticity in Rat Prefrontal Cortex

    PubMed Central

    Goriounova, Natalia A.; Mansvelder, Huibert D.

    2013-01-01

    Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age can compromise the normal course of prefrontal development and lead to cognitive impairments in later life. Recently, we reported that nicotine exposure during adolescence results in a short-term increase and lasting reduction in synaptic mGluR2 levels in the rat mPFC, causing attention deficits during adulthood. It is unknown how changed synaptic mGluR2 levels after adolescent nicotine exposure affect the ability of mPFC synapses to undergo long-term synaptic plasticity. Here, we addressed this question. To model nicotine exposure, adolescent (P34–P43) or adult (P60–P69) rats were treated with nicotine injections three times per day for 10 d. We found that, both during acute activation of nicotinic receptors in the adolescent mPFC as well as immediately following nicotine treatment during adolescence, long-term plasticity in response to timed presynaptic and postsynaptic activity (tLTP) was strongly reduced. In contrast, in the mPFC of adult rats 5 weeks after they received nicotine treatment during adolescence, but not during adulthood, tLTP was increased. Short-and long-term adaptation of mPFC synaptic plasticity after adolescent nicotine exposure could be explained by changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, whereas activating mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure to nicotine during adolescence alters the rules for spike timing-dependent plasticity in prefrontal networks that may explain the observed deficits in cognitive performance in later life. PMID:22855798

  4. Adolescent nicotine induces persisting changes in development of neural connectivity.

    PubMed

    Smith, Robert F; McDonald, Craig G; Bergstrom, Hadley C; Ehlinger, Daniel G; Brielmaier, Jennifer M

    2015-08-01

    Adolescent nicotine induces persisting changes in development of neural connectivity. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into adulthood. Areas sensitive to, and not sensitive to, structural remodeling induced by adolescent nicotine suggest that the remodeling generally corresponds to the extended amygdala. Evidence suggests that dendritic remodeling is accompanied by persisting changes in synaptic connectivity. Modeling, electrophysiological, neurochemical, and behavioral data are consistent with the implication of our anatomical studies showing that adolescent nicotine induces persisting changes in neural connectivity. Emerging data thus suggest that early adolescence is a period when nicotine consumption, presumably mediated by nicotine-elicited changes in patterns of synaptic activity, can sculpt late brain development, with consequent effects on synaptic interconnection patterns and behavior regulation. Adolescent nicotine may induce a more addiction-prone phenotype, and the structures altered by nicotine also subserve some emotional and cognitive functions, which may also be altered. We suggest that dendritic elaboration and associated changes are mediated by activity-dependent synaptogenesis, acting in part

  5. 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

  6. 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

  7. Genetic Risk For Nicotine Dependence in the Cholinergic System and Activation of the Brain Reward System in Healthy Adolescents

    PubMed Central

    Nees, F; Witt, S H; Lourdusamy, A; Vollstädt-Klein, S; Steiner, S; Poustka, L; Banaschewski, T; Barker, G J; Büchel, C; Conrod, P J; Frank, J; Gallinat, J; Garavan, H; Heinz, A; Ittermann, B; Loth, E; Mann, K; Artiges, E; Paus, T; Pausova, Z; Smolka, M N; Struve, M; Schumann, G; Rietschel, M; Flor, H

    2013-01-01

    Genetic variation in a genomic region on chromosome 15q25.1, which encodes the alpha5, alpha3, and beta4 subunits of the cholinergic nicotinic receptor genes, confers risk to smoking and nicotine dependence (ND). Neural reward-related responses have previously been identified as important factors in the development of drug dependence involving ND. Applying an imaging genetics approach in two cohorts (N=487; N=478) of healthy non-smoking adolescents, we aimed to elucidate the impact of genome-wide significant smoking-associated variants in the CHRNA5–CHRNA3–CHRNB4 gene cluster on reward-related neural responses in central regions such as the striatum, orbitofrontal and anterior cingulate cortex (ACC), and personality traits related to addiction. In both samples, carriers of the rs578776 GG compared with AG/AA genotype showed a significantly lower neural response to reward outcomes in the right ventral and dorsal ACC but not the striatum or the orbitofrontal cortex. Rs578776 was unrelated to neural reward anticipation or reward magnitude. Significantly higher scores of anxiety sensitivity in GG compared with AG/AA carriers were found only in sample 1. Associations with other personality traits were not observed. Our findings suggest that the rs578776 risk variant influences susceptibility to ND by dampening the response of the ACC to reward feedback, without recruiting the striatum or orbitofrontal cortex during feedback or anticipation. Thus, it seems to have a major role in the processing of and behavioral adaptation to changing reward outcomes. PMID:23689675

  8. Genetic risk for nicotine dependence in the cholinergic system and activation of the brain reward system in healthy adolescents.

    PubMed

    Nees, F; Witt, S H; Lourdusamy, A; Vollstädt-Klein, S; Steiner, S; Poustka, L; Banaschewski, T; Barker, G J; Büchel, C; Conrod, P J; Frank, J; Gallinat, J; Garavan, H; Heinz, A; Ittermann, B; Loth, E; Mann, K; Artiges, E; Paus, T; Pausova, Z; Smolka, M N; Struve, M; Schumann, G; Rietschel, M; Flor, H

    2013-10-01

    Genetic variation in a genomic region on chromosome 15q25.1, which encodes the alpha5, alpha3, and beta4 subunits of the cholinergic nicotinic receptor genes, confers risk to smoking and nicotine dependence (ND). Neural reward-related responses have previously been identified as important factors in the development of drug dependence involving ND. Applying an imaging genetics approach in two cohorts (N=487; N=478) of healthy non-smoking adolescents, we aimed to elucidate the impact of genome-wide significant smoking-associated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on reward-related neural responses in central regions such as the striatum, orbitofrontal and anterior cingulate cortex (ACC), and personality traits related to addiction. In both samples, carriers of the rs578776 GG compared with AG/AA genotype showed a significantly lower neural response to reward outcomes in the right ventral and dorsal ACC but not the striatum or the orbitofrontal cortex. Rs578776 was unrelated to neural reward anticipation or reward magnitude. Significantly higher scores of anxiety sensitivity in GG compared with AG/AA carriers were found only in sample 1. Associations with other personality traits were not observed. Our findings suggest that the rs578776 risk variant influences susceptibility to ND by dampening the response of the ACC to reward feedback, without recruiting the striatum or orbitofrontal cortex during feedback or anticipation. Thus, it seems to have a major role in the processing of and behavioral adaptation to changing reward outcomes. PMID:23689675

  9. 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

  10. 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. PMID:27068856

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats.

    PubMed

    Gellner, Candice A; Belluzzi, James D; Leslie, Frances M

    2016-10-01

    Although smoking initiation typically occurs during adolescence, most preclinical studies of tobacco use involve adult animals. Furthermore, their focus is largely on nicotine alone, even though cigarette smoke contains thousands of constituents. The present study therefore aimed to determine whether aqueous constituents in cigarette smoke affect acquisition of nicotine self-administration during adolescence in rats. Adolescent and adult male rats, aged postnatal day (P) 25 and 85, respectively, were food trained on a fixed ratio 1 (FR1) schedule, then allowed to self-administer one of 5 doses of nicotine (0, 3.75, 7.5, 15, or 30 μg/kg) or aqueous cigarette smoke extract (CSE) with equivalent nicotine content. Three progressively more difficult schedules of reinforcement, FR1, FR2, and FR5, were used. Both adolescent and adult rats acquired self-administration of nicotine and CSE. Nicotine and CSE similarly increased non-reinforced responding in adolescents, leading to enhanced overall drug intake as compared to adults. When data were corrected for age-dependent alterations in non-reinforced responding, adolescents responded more for low doses of nicotine and CSE than adults at the FR1 reinforcement schedule. No differences in adolescent responding for the two drugs were seen at this schedule, whereas adults had fewer responses for CSE than for nicotine. However, when the reinforcement schedule was increased to FR5, animals dose-dependently self-administered both nicotine and CSE, but no drug or age differences were observed. These data suggest that non-nicotine tobacco smoke constituents do not influence the reinforcing effect of nicotine in adolescents. PMID:27346207

  17. Vulnerability to nicotine self-administration in adolescent mice correlates with age-specific expression of α4* nicotinic receptors.

    PubMed

    Renda, Anthony; Penty, Nora; Komal, Pragya; Nashmi, Raad

    2016-09-01

    The majority of smokers begin during adolescence, a developmental period with a high susceptibility to substance abuse. Adolescents are affected differently by nicotine compared to adults, with adolescents being more vulnerable to nicotine's rewarding properties. It is unknown if the age-dependent molecular composition of a younger brain contributes to a heightened susceptibility to nicotine addiction. Nicotine, the principle pharmacological component of tobacco, binds and activates nicotinic acetylcholine receptors (nAChRs) in the brain. The most prevalent is the widely expressed α4-containing (α4*) subtype which mediates reward and is strongly implicated in nicotine dependence. Exposing different age groups of mice, postnatal day (P) 44-86 days old, to a two bottle-choice oral nicotine self-administration paradigm for five days yielded age-specific consumption levels. Nicotine self-administration was elevated in the P44 group, peaked at P54-60 and was drastically lower in the P66 through P86 groups. We also quantified α4* nAChR expression via spectral confocal imaging of brain slices from α4YFP knock-in mice, in which the α4 nAChR subunit is tagged with a yellow fluorescent protein. Quantitative fluorescence revealed age-specific α4* nAChR expression in dopaminergic and GABAergic neurons of the ventral tegmental area. Receptor expression showed a strong positive correlation with daily nicotine dose, suggesting that α4* nAChR expression levels are age-specific and may contribute to the propensity to self-administer nicotine. PMID:27102349

  18. Cognitive Function During Nicotine Withdrawal: Implications for Nicotine Dependence Treatment

    PubMed Central

    Ashare, Rebecca L.; Falcone, Mary; Lerman, Caryn

    2013-01-01

    Nicotine withdrawal is associated with deficits in neurocognitive function including sustained attention, working memory, and response inhibition. Several convergent lines of evidence suggest that these deficits may represent a core dependence phenotype and a target for treatment development efforts. A better understanding of the mechanisms underlying withdrawal-related cognitive deficits may lead to improve nicotine dependence treatment. We begin with an overview of the neurocognitive effects of withdrawal in rodent and human models, followed by discussion of the neurobehavioral mechanisms that are thought to underlie these effects. We then review individual differences in withdrawal-related neurocognitive effects including genetics, gender, and psychiatric comorbidity. We conclude with a discussion of the implications of this research for developing improved therapies, both pharmacotherapy and behavioral treatments, that target cognitive symptoms of nicotine withdrawal. PMID:23639437

  19. 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

  20. Locomotor and Stress Responses to Nicotine Differ in Adolescent and Adult Rats

    PubMed Central

    Cao, Junran; Belluzzi, James D.; Loughlin, Sandra E.; Dao, Jasmin M.; Chen, YiLing; Leslie, Frances M.

    2010-01-01

    Since adolescence is a critical period for the initiation of tobacco use, we have systematically compared behavioral and endocrine responses to nicotine in Sprague-Dawley rats of both sexes at early adolescence (postnatal day (P) 28), mid- adolescence (P38) and adulthood (P90). Locomotion and center time in a novel open field were evaluated for 30 min following intravenous injection of saline or nicotine (60 µg/kg), followed by measurement of plasma corticosterone. Complex age and sex differences in behavioral and endocrine response were observed, which were dependent on the functional endpoint examined. Whereas there were age differences in nicotine effects on all functional measures, sex differences were largely restricted to adult stress-related corticosterone and center-time responses. Although significant drug effects were detected at P28 and P90, there was no effect of nicotine at P38 on any measure examined. In saline-treated males, but not females, there were significant positive correlations across age between initial ambulatory counts and both initial vertical counts and total center time. Nicotine treatment increased correlations in both sexes, and yielded a significant negative interaction between initial ambulatory counts and plasma corticosterone. The unique responses of adolescents to nicotine are consistent with an immature function of nicotinic acetylcholine receptors at this age. PMID:20423718

  1. Single trial nicotine conditioned place preference in pre-adolescent male and female rats.

    PubMed

    Edwards, Alexander W; Konz, Nathan; Hirsch, Zahava; Weedon, Jeremy; Dow-Edwards, Diana L

    2014-10-01

    The mean age of first voluntary tobacco inhalation is 12.3 years (DiFranza et al., 2004). 60% of smokers start smoking before the age of 14 and 90% are dependent before reaching the age of 19. Females are typically more sensitive to nicotine than males yet few studies examine the effects of nicotine on the reward systems in pre-adolescent female subjects. This study utilized the single trial conditioned place preference (CPP) test in very young (postnatal day 25-27) rats of both sexes. Latent effects on anxiety and amphetamine response were determined 5 and 7 days following a second nicotine exposure. Results show that 0.05 mg/kg nicotine induced CPP in females following a single trial while both sexes showed CPP following the 0.5 mg/kg dose. Five days later, rats dosed with 0.05 mg/kg show increased time on the open arm of the elevated plus maze, an anxiolytic response. While baseline activity was increased in nicotine-exposed males 7 days following dosing, amphetamine response was not affected by the treatments in either sex. Therefore, our data suggest that young females are more sensitive to nicotine reward than males supporting a heightened sensitivity of the mesolimbic dopamine system in very young females. However, alterations in baseline activity were only seen in males suggesting that different components of the system are affected by nicotine in each sex. An anxiolytic response to nicotine 5 days after dosing may suggest that this very young age group is uniquely affected by this very low nicotine dose. Clearly, nicotine has substantial acute and lasting effects during pre-adolescence at doses substantially lower than seen at older ages as reported by others. These effects, which could potentially result from cigarette or e-cigarette smoking by 11-12 year old children , focus attention on the vulnerability of this age group to nicotine. PMID:25109273

  2. 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

  3. Nicotine Dependence Reveals Distinct Responses from Neurons and Their Resident Nicotinic Receptors in Medial Habenula.

    PubMed

    Shih, Pei-Yu; McIntosh, J Michael; Drenan, Ryan M

    2015-12-01

    Nicotinic acetylcholine receptors (nAChRs) are the molecular target of nicotine. nAChRs in the medial habenula (MHb) have recently been shown to play a role in nicotine dependence, but it is not clear which nAChR subtypes or MHb neuron types are most important. To identify MHb nAChRs and/or cell types that play a role in nicotine dependence, we studied these receptors and cells with brain slice electrophysiology using both acute and chronic nicotine application. Cells in the ventroinferior (MHbVI) and ventrolateral MHb (MHbVL) subregions expressed functional nAChRs with different pharmacology. Further, application of nicotine to cells in these subregions led to different action potential firing patterns. The latter result was correlated with a differing ability of nicotine to induce nAChR desensitization. Chronic nicotine caused functional upregulation of nAChRs selectively in MHbVI cells, but did not change nAChR function in MHbVL. Importantly, firing responses were also differentially altered in these subregions following chronic nicotine. MHbVI neurons treated chronically with nicotine exhibited enhanced basal pacemaker firing but a blunted nicotine-induced firing response. MHbVL neurons did not change their firing properties in response to chronic nicotine. Together, these results suggest that acute and chronic nicotine differentially affect nAChR function and output of cells in MHb subregions. Because the MHb extensively innervates the interpeduncular nucleus, an area critical for both affective and somatic signs of withdrawal, these results could reflect some of the neurophysiological changes thought to occur in the MHb to the interpeduncular nucleus circuit in human smokers. PMID:26429939

  4. Nicotine vaccines to treat tobacco dependence

    PubMed Central

    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. PMID:23108361

  5. 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

  6. 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…

  7. Adolescent mice are less sensitive to the effects of acute nicotine on context pre-exposure than adults.

    PubMed

    Kutlu, Munir Gunes; Braak, David C; Tumolo, Jessica M; Gould, Thomas J

    2016-07-01

    Adolescence is a critical developmental period associated with both increased vulnerability to substance abuse and maturation of certain brain regions important for learning and memory such as the hippocampus. In this study, we employed a hippocampus-dependent learning context pre-exposure facilitation effect (CPFE) paradigm in order to test the effects of acute nicotine on contextual processing during adolescence (post-natal day (PND) 38) and adulthood (PND 53). In Experiment 1, adolescent or adult C57BL6/J mice received either saline or one of three nicotine doses (0.09, 0.18, and 0.36mg/kg) prior to contextual pre-exposure and testing. Our results demonstrated that both adolescent and adult mice showed CPFE in the saline groups. However, adolescent mice only showed acute nicotine enhancement of CPFE with the highest nicotine dose whereas adult mice showed the enhancing effects of acute nicotine with all three doses. In Experiment 2, to determine if the lack of nicotine's effects on CPFE shown by adolescent mice is specific to the age when they are tested, mice were either given contextual pre-exposure during adolescence or adulthood and received immediate shock and testing during adulthood after a 15day delay. We found that both adolescent and adult mice showed CPFE in the saline groups when tested during adulthood. However, like Experiment 1, mice that received contextual pre-exposure during adolescence did not show acute nicotine enhancement except at the highest dose (0.36mg/kg) whereas both low (0.09mg/kg) and high (0.36mg/kg) doses enhanced CPFE in adult mice. Finally, we showed that the enhanced freezing response found with 0.36mg/kg nicotine in the 15-day experiment may be a result of decreased locomotor activity as mice that received this dose of nicotine traveled shorter distances in an open field paradigm. Overall, our results indicate that while adolescent mice showed normal contextual processing when tested both during adolescence and adulthood, they

  8. 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

  9. 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:…

  10. [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

  11. Nicotine dependence, abuse, and craving: dimensionality in an Israeli sample

    PubMed Central

    Shmulewitz, Dvora; Keyes, Katherine M.; Wall, Melanie M.; Aharonovich, Efrat; Aivadyan, Christina; Greenstein, Eliana; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Grant, Bridget F.; Hasin, Deborah

    2011-01-01

    Aims Evidence-based changes planned for DSM-5 substance use disorders (SUDs) include combining dependence and three of the abuse criteria into one disorder and adding a criterion indicating craving. Because DSM-IV did not include a category for nicotine abuse, little empirical support is available for aligning the nicotine use disorder criteria with the DSM-5 criteria for other SUDs. Design Latent variable analyses, likelihood ratio tests (LRT) and bootstrap tests were used to explore the unidimensionality, psychometric properties and information of the nicotine criteria. Setting, Participants A sample of household residents selected from the Israeli population register yielded 727 lifetime cigarette smokers. Measurements DSM-IV nicotine dependence criteria and proposed abuse and craving criteria, assessed with a structured interview. Findings Three abuse criteria (hazardous use, social/interpersonal problems, and neglect roles) were prevalent among smokers, formed a unidimensional latent trait with nicotine dependence criteria, were intermixed with dependence criteria across the severity spectrum, and significantly increased the diagnostic information over the dependence-only model. LRT results also supported including the abuse criteria (Χ23=259.63, p<0.0001). A craving criterion was shown to fit well with the other criteria. Conclusion Similar to findings from research on other substances, nicotine dependence, abuse, and craving criteria formed a single factor. The results support alignment of nicotine criteria with those for alcohol and drug use disorders in DSM-5. PMID:21545668

  12. Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans

    PubMed Central

    Saccone, Nancy L.; Schwantes-An, Tae-Hwi; Wang, Jen C.; Grucza, Richard A.; Breslau, Naomi; Hatsukami, Dorothy; Johnson, Eric O.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2010-01-01

    Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer, and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect risk for nicotine dependence in a new sample of African-Americans (N = 710). We also analyzed this African-American sample together with a European-American sample (N=2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non-dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7, and CHRNA10 show modest association with nicotine dependence risk in the African-American sample. In addition, CHRNA4, CHRNB3-CHRNA6, and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor SNPs that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the African-American sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in European-Americans and also 1.9% in African-Americans; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside of chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations. PMID:20584212

  13. 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

  14. 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

  15. 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

  16. Menthol's potential effects on nicotine dependence: a tobacco industry perspective

    PubMed Central

    2011-01-01

    Objective To examine what the tobacco industry knows about the potential effects menthol may have on nicotine dependence. Methods A snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu/) between 22 February and 29 April, 2010. Of the approximately 11 million documents available in the Legacy Tobacco Documents Library, the iterative searches returned tens of thousands of results. We qualitatively analysed a final collection of 309 documents relevant the effects of menthol on nicotine dependence. Results The tobacco industry knows that menthol overrides the harsh taste of tobacco and alleviates nicotine's irritating effects, synergistically interacts with nicotine, stimulates the trigeminal nerve to elicit a ‘liking’ response for a tobacco product, and makes low tar, low nicotine tobacco products more acceptable to smokers than non-mentholated low delivery products. Conclusion Menthol is not only used in cigarettes as a flavour additive; tobacco companies know that menthol also has sensory effects and interacts with nicotine to produce tobacco products that are easier to smoke, thereby making it easier to expose smokers, especially those who are new and uninitiated, to the addictive power of nicotine. PMID:21504929

  17. Neuronal Nicotinic Acetylcholine Receptors: Common Molecular Substrates of Nicotine and Alcohol Dependence

    PubMed Central

    Hendrickson, Linzy M.; Guildford, Melissa J.; Tapper, Andrew R.

    2013-01-01

    Alcohol and nicotine are often co-abused. As many as 80–95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels normally activated by endogenous acetylcholine (ACh), ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic) reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA) which project to the nucleus accumbens (NAc). Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from pre-clinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence. PMID:23641218

  18. Sex Differences in Adult Cognitive Deficits after Adolescent Nicotine Exposure in Rats

    PubMed Central

    Pickens, Laura R. G.; Rowan, James D.; Bevins, Rick A.; Fountain, Stephen B.

    2013-01-01

    This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood. PMID:23673345

  19. Dissection of the Phenotypic and Genotypic Associations With Nicotinic Dependence

    PubMed Central

    Baker, Timothy B.; Grucza, Richard; Wang, Jen C.; Johnson, Eric O.; Breslau, Naomi; Hatsukami, Dorothy; Smith, Stevens S.; Saccone, Nancy; Saccone, Scott; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2012-01-01

    Introduction: Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures. Methods: Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls). Nicotine dependence was assessed with multiple smoking measures, including the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual for Mental Disorders-IV (DSM-IV) nicotine dependence, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Single-item measures of cigarettes per day (CPD) and time to first cigarette (TTF) in the morning were also examined. Results: Among the variants, association effect sizes were largest for rs16969968, with measures of craving and heavy smoking, especially cigarettes smoked per day, showing the largest effects. Significant but weaker associations were found for rs6474412 and rs3733729 but not for rs1329650. None of the more comprehensive measures of smoking behaviors yielded stronger genetic associations with these variants than did CPD. Conclusions: CPD is an important simple measure that captures in part the genetic associations of CHRNA5 and nicotine dependence, even when other more comprehensive measures of smoking behaviors are examined. The CHRNA5 gene is associated with heavy compulsive smoking and craving; this should inform the mission to improve the diagnostic validity of DSM-V. PMID:22102629

  20. Tobacco Harm Reduction and the Evolution of Nicotine Dependence

    PubMed Central

    2011-01-01

    In recent years, a renewed debate has developed around the potential for modified tobacco products to play a role in reducing tobacco-related harm. During the 1960s and 1970s medical experts recommended to smokers who could not quit that they switch to cigarettes with lower tar and nicotine content. At the time, survey data suggested that smokers who switched did not compensate for the reduction in nicotine by increasing their intake. However, public health scientists were hindered in their ability to evaluate the population impact of the reduced tar strategy by a limited understanding of nicotine addiction. Smoking dependence was seen as primarily psychological and social, rather than pharmacological or biological, until the late 1970s, when addiction researchers began to apply experimental techniques from other forms of drug abuse to study smoking behavior. This history has important lessons for current discussions about tobacco harm reduction and regulation of nicotine delivery. PMID:21330596

  1. Cannabinoid Receptor 1 Gene Association With Nicotine Dependence

    PubMed Central

    Chen, Xiangning; Williamson, Vernell S.; An, Seon-Sook; Hettema, John M.; Aggen, Steven H.; Neale, Michael C.; Kendler, Kenneth S.

    2009-01-01

    Context The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence. Objective To test the hypothesis that the CNR1 gene is associated with nicotine dependence. Design Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n=688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerström Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry. Participants White patients aged 18 to 65 years who met the criteria of inclusion. Main Outcome Measures Fagerström Tolerance Questionnaire and FTND scores. Results Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P<.001 and P = .009, respectively). Conclusion Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific. PMID:18606954

  2. Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2016-07-01

    Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28-53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking. PMID:25950618

  3. Clarifying the Relationship between Impulsive Delay Discounting and Nicotine Dependence

    PubMed Central

    Amlung, Michael; MacKillop, James

    2014-01-01

    Impulsive delayed reward discounting (DRD) has been linked to nicotine dependence, but with some inconsistency. This may be related to the considerable variability in the literature with regard to the DRD assessments used, particularly in the case of reward magnitudes assessed. In addition, previous studies have often not considered concurrent substance use when examining the relationship between DRD and nicotine dependence. The current study sought to further clarify the relationship between DRD and nicotine dependence by characterizing DRD across diverse reward magnitudes and incorporating other substance use. Daily smokers (N = 933) were assessed for DRD preferences across nine reward magnitudes (delayed reward range: $2.50–$850), comorbid substance use, and relevant demographic variables (age, education, income). A significant large effect size magnitude effect was found for DRD, reflecting steeper discounting for smaller delayed rewards, but significant correlations across magnitudes also suggested similar relative levels of discounting. Principal components analysis (PCA) was used to generate a single latent index of discounting across all magnitudes that accounted for 67% of the total variance. In both correlation and regression analyses, steeper composite DRD was significantly associated with nicotine dependence severity. This relationship remained statistically significant after incorporating demographic variables and alcohol and illicit drug use. These findings provide evidence of a specific link between impulsive DRD and nicotine dependence, and reveal that this association is robust across a broad range of monetary rewards. The study also demonstrates the utility of using PCA to generate latent indices of delay discounting across multiple magnitudes of delayed reward. PMID:24841186

  4. Clarifying the relationship between impulsive delay discounting and nicotine dependence.

    PubMed

    Amlung, Michael; MacKillop, James

    2014-09-01

    Impulsive delayed reward discounting (DRD) has been linked to nicotine dependence, but with some inconsistency. This may be related to the considerable variability in the literature with regard to the DRD assessments used, particularly in the case of the reward magnitudes assessed. In addition, previous studies have often not considered concurrent substance use when examining the relationship between DRD and nicotine dependence. The current study sought to further clarify the relationship between DRD and nicotine dependence by characterizing DRD across diverse reward magnitudes and incorporating other substance use. Daily smokers (N = 933) were assessed for DRD preferences across nine reward magnitudes (delayed reward range: $2.50-$850), comorbid substance use, and relevant demographic variables (age, education, income). A significant large effect size magnitude effect was found for DRD, reflecting steeper discounting for smaller delayed rewards, but significant correlations across magnitudes also suggested similar relative levels of discounting. Principal components analysis (PCA) was used to generate a single latent index of discounting across all magnitudes that accounted for 69% of the total variance. In correlation and regression analyses, steeper composite DRD was significantly associated with nicotine dependence severity. This relationship remained statistically significant after incorporating demographic variables and alcohol and illicit drug use. These findings provide evidence of a specific link between impulsive DRD and nicotine dependence and reveal that this association is robust across a broad range of monetary rewards. The study also demonstrates the utility of using PCA to generate latent indices of delay discounting across multiple magnitudes of delayed reward. PMID:24841186

  5. Conditioned Place Preference and Self-Administration Induced by Nicotine in Adolescent and Adult Rats

    PubMed Central

    Ahsan, Hafiz Muhammad; de la Peña, June Bryan I.; Botanas, Chrislean Jun; Kim, Hee Jin; Yu, Gu Yong; Cheong, Jae Hoon

    2014-01-01

    Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine. PMID:25414778

  6. Conditioned place preference and self-administration induced by nicotine in adolescent and adult rats.

    PubMed

    Ahsan, Hafiz Muhammad; de la Peña, June Bryan I; Botanas, Chrislean Jun; Kim, Hee Jin; Yu, Gu Yong; Cheong, Jae Hoon

    2014-09-01

    Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine. PMID:25414778

  7. 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

  8. Association of withdrawal features with nicotine dependence as measured by the Fagerström Test for Nicotine Dependence (FTND)

    PubMed Central

    Ríos-Bedoya, Carlos F.; Snedecor, Sandy M.; Pomerleau, Cynthia S.; Pomerleau, Ovide F.

    2008-01-01

    The aim of this study is to advance our understanding of how nicotine dependence level, defined by the Fagerström Test of Nicotine Dependence (FTND), relates to nicotine withdrawal features. We classified nicotine dependence in two categories, 1) low dependence (LD; FTND <4) and 2) high dependence (HD; FTND ≥4). A sample of 241 smokers was recruited via newspaper ads and public notices. Using a multivariate response model with adjustments for age, sex, age at first cigarette, race, and current or past history of depression, we observed a small to modest statistically robust association between nicotine dependence level and withdrawal features such as, irritation/anger (adjusted relative risk, aRR = 1.2; 95% CI 1.00, 1.3); nervousness (aRR = 1.3; 95% CI 1.1, 1.6); restlessness (aRR = 1.2; 95% CI 1.1, 1.4); difficulty concentrating (aRR = 1.3; 95% CI 1.1, 1.7); and trouble sleeping (aRR = 1.8; 95% CI 1.2, 2.6). Our findings are consistent with the inference that the FTND measures “physiological dependence” and that multidimensional approaches are needed to capture the full range of smoking phenotypology. PMID:18502052

  9. 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

  10. The Nicotine Dependence Syndrome Scale in Finnish Smokers

    PubMed Central

    Broms, Ulla; Madden, Pamela A.F.; Heath, Andrew C.; Pergadia, Michele L.; Shiffman, Saul; Kaprio, Jaakko

    2007-01-01

    The Nicotine Dependence Syndrome Scale (NDSS) is a new multidimensional measure of nicotine dependence. The study aim was to examine the structure and heritability of the NDSS and its associations with nicotine dependence defined by FTND and DSM-IV criteria among Finnish smokers participating in an ongoing twin-family study. Adult twin pairs concordant for smoking from the Finnish Twin Cohort Study, and their siblings and parents were interviewed. Among 1370 smokers, the NDSS sum score (a summary measure of dependence) correlated moderately high with FTND score (r=0.62). Subjects in the highest NDSS sum score groups were more likely to be nicotine dependent according to DSM-IV criteria compared with those in the lowest quintile (odds ratio = 36.7, 95% Confidence interval 13.0–103). In exploratory factor analysis we derived three factors, named drive/priority, stereotypy/continuity and tolerance. The drive/priority factor correlated best with FTND (r=0.54). Genetic modelling showed no differences in the genetic architecture of NDSS or FTND by gender; the overall heritability estimate for NDSS was 0.30 (95% CI 0.06–0.47), and for FTND 0.40 (95% CI 0.23–0.55) The NDSS sum score is moderately high associated with DSM-IV nicotine dependence as well as FTND. These analyses indicate that the NDSS functions well in a Finnish family-based sample and provide additional validation of a new scale developed to capture complex behavioral features of nicotine dependence. PMID:17174039

  11. 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

  12. Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

    PubMed Central

    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. PMID:25477708

  13. Sex differences in yohimbine-induced increases in the reinforcing efficacy of nicotine in adolescent rats.

    PubMed

    Li, Sophia; Zou, Sheng; Coen, Kathleen; Funk, Douglas; Shram, Megan J; Lê, A D

    2014-03-01

    Stress is an important factor in the initiation and maintenance of smoking in adolescents. Women are more vulnerable to the development of addiction to smoking and have more difficulty quitting than men. Women also showe enhanced responses to stress. Despite these differences, no work has been done examining the effects of stress on the reinforcing efficacy of self-administered nicotine in adolescent rats, or if there are sex differences. Male and female adolescent Long Evans rats were trained to self-administer one of three different intravenous doses of nicotine (7.5, 15, 30 μg/kg/infusion) first on fixed ratio, and then on a progressive ratio (PR) schedule beginning on postnatal day 33. The effect of the pharmacological stressor yohimbine (0.3, 0.6 mg/kg, i.p.) on the reinforcing efficacy of nicotine was then determined using the PR schedule. Yohimbine stimulated nicotine intake and increased PR breakpoints and numbers of infusions received in both male and female adolescent rats. The infusion dose of nicotine was positively associated with yohimbine-induced increases in responding. Female rats showed significantly increased breakpoints at yohimbine doses and nicotine infusion doses at which males did not. The effects of the pharmacological stressor, yohimbine on the reinforcing efficacy of nicotine are therefore linked to sex and nicotine infusion dose. Female rats are more sensitive to stress-induced potentiation of nicotine self-administration. PMID:22784103

  14. 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…

  15. General and Specific Predictors of Nicotine and Alcohol Dependence in Early Adulthood: Genetic and Environmental Influences

    PubMed Central

    Samek, Diana R; Keyes, Margaret A; Hicks, Brian M; Bailey, Jennifer; McGue, Matt; Iacono, William G

    2014-01-01

    Objective: This study builds on previous work delineating a hierarchical model of family environmental risk in relation to a hierarchical model of externalizing disorders (EXTs) by evaluating for gene–environment interplay in these relationships. The associations between parent–child relationship quality (conflict, bonding, and management) and substance-specific adolescent family environments (parental/sibling tobacco/alcohol use) in relation to young adult EXTs (age ∼22 years nicotine, alcohol, and other drug dependence; antisocial and risky sexual behavior) were evaluated. Method: The sample included 533 adopted offspring and 323 biological offspring. Because adopted youth do not share genes with their parents, a significant association between parent–child relationship quality and EXTs would provide evidence against passive gene–environment correlation (rGE). Significant associations between parental tobacco/alcohol use in relation to offspring nicotine/alcohol dependence in the adopted offspring support common environmental influence. Significant associations detected for the biological offspring only suggest common genetic influence. Results: For both adoptive and biological offspring, there was a significant association between parent–child relationship quality and EXTs. Parental tobacco/alcohol use was unrelated to EXTs. Sibling tobacco/alcohol use was related to EXTs, but only for the biological siblings. Parental tobacco use was associated with the residual variance in nicotine dependence in adopted offspring. Conclusions: Findings replicate a long-term influence of adolescent parent–child relationship quality on adult EXTs. Findings extend previous research by providing evidence against passive rGE in this association. The association between parental tobacco use and adult nicotine dependence appears to be environmentally mediated, but caution is warranted as we found this relationship only for adopted youth. PMID:24988261

  16. 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

  17. 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. PMID:26428091

  18. 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

  19. Nicotine-induced plasma corticosterone is attenuated by social interactions in male and female adolescent rats.

    PubMed

    Pentkowski, N S; Painter, M R; Thiel, K J; Peartree, N A; Cheung, T H C; Deviche, P; Adams, M; Alba, J; Neisewander, J L

    2011-11-01

    Most smokers begin smoking during adolescence, a period during which social reward is highly influential. Initial exposure to nicotine can produce anxiogenic effects that may be influenced by social context. This study examined play behavior and plasma corticosterone following nicotine administration (0.6 mg/kg, s.c.) in both male and female adolescent (PND39) Sprague-Dawley rats in either isolate or social contexts. In blood samples collected immediately following the 15-min test session, nicotine increased plasma corticosterone relative to saline in both male and female isolate rats, but failed to do so in both males and females placed together in same-sex pairs. Nicotine also attenuated several indices of play behavior including nape attacks, pins and social contact. In isolate rats, nicotine selectively increased locomotor activity in females; however, when administered to social pairs, nicotine decreased locomotion in both sexes. These findings suggest that the presence of a social partner may decrease the initial negative, stress-activating effects of nicotine, perhaps leading to increased nicotine reward. PMID:21782841

  20. Nicotine-induced plasma corticosterone is attenuated by social interactions in male and female adolescent rats

    PubMed Central

    Pentkowski, N.S.; Painter, M.R.; Thiel, K.J.; Peartree, N.A.; Cheung, T.H.C.; Deviche, P.; Adams, M.; Alba, J.; Neisewander, J.L.

    2011-01-01

    Most smokers begin smoking during adolescence, a period during which social reward is highly influential. Initial exposure to nicotine can produce anxiogenic effects that may be influenced by social context. This study examined play behavior and plasma corticosterone following nicotine administration (0.6 mg/kg, s.c.) in both male and female adolescent (PND39) Sprague-Dawley rats in either isolate or social contexts. In blood samples collected immediately following the 15-min test session, nicotine increased plasma corticosterone relative to saline in both male and female isolate rats, but failed to do so in both males and females placed together in same-sex pairs. Nicotine also attenuated several indices of play behavior including nape attacks, pins and social contact. In isolate rats, nicotine selectively increased locomotor activity in females; however, when administered to social pairs, nicotine decreased locomotion in both sexes. These findings suggest that the presence of a social partner may decrease the initial negative, stress-activating effects of nicotine, perhaps leading to increased nicotine reward. PMID:21782841

  1. Nicotine Effects in Adolescence and Adulthood on Cognition and α4β2-Nicotinic Receptors in the Neonatal Ventral Hippocampal Lesion Rat Model of Schizophrenia

    PubMed Central

    Berg, Sarah A.; Sentir, Alena M.; Bell, Richard L.; Engleman, Eric A.; Chambers, R. Andrew

    2014-01-01

    Rational Nicotine use in schizophrenia has traditionally been explained as ‘self-medication’ of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods Nicotine transdermal patch (5 mg/kg/day vs. placebo × 10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food–reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p<0.05) but not ventral striatum (<5% changes, p>.40), whereas nicotine history elevated nAChRs across both regions (>30%, p<0.001) without interacting with NVHLs. Adolescent vs. adult nicotine exposure did not alter nAChRs differentially. Conclusions Although replicating nicotine-induced up-regulation of nAChRs in human smokers and demonstrating NVHL validity in terms of schizophrenia-associated nAChR density patterns, these findings do not support hypotheses explaining increased nicotine use in schizophrenia as reflecting illness-specific effects of nicotine to therapeutically alter cognition or nAChR densities. PMID:25388292

  2. Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response.

    PubMed

    Mojica, Celina Y; Dao, Jasmin M; Yuan, Menglu; Loughlin, Sandra E; Leslie, Frances M

    2014-02-01

    Adolescence is a sensitive developmental period for limbic and dopamine systems that coincides with the typical age for onset of tobacco use. We have previously shown that a 4-day, low-dose nicotine (0.06 mg/kg) pretreatment enhances locomotor and penile response to the D2-like agonist, quinpirole (0.4 mg/kg), in adolescent but not adult rats. The present study is designed to determine mechanisms underlying this effect. Nicotine enhancement of adolescent quinpirole-induced locomotion was mediated by D2 receptors (D2Rs) since it was blocked by the D2R antagonist, L-741,626, but not by the D3R and D4R antagonists, NGB 2904 and L-745,870. Enhancement of quinpirole-induced erectile response was blocked by both L-741,626 and NGB 2904, indicating involvement of D3Rs. Whereas D2R binding was unaffected by adolescent nicotine pretreatment, effector coupling in the striatum was increased, as determined by GTPγS binding. Nicotine pretreatment enhanced quinpirole-induced c-fos mRNA expression in the hypothalamic paraventricular and supraoptic nuclei in adolescents only. Adolescent nicotine pretreatment enhanced c-fos mRNA expression in corticotropin releasing factor (CRF) cells of the paraventricular nucleus, and enhancement of penile erection was blocked by the CRF-1 receptor antagonist, CP 376,396. These findings suggest that adolescent dopamine and CRF systems are vulnerable to alteration by nicotine. This is the first evidence for a role of CRF in adolescent erectile response. PMID:24157491

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

    PubMed Central

    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. PMID:26039516

  4. Nicotine alters limbic function in adolescent rat by a 5-HT1A receptor mechanism.

    PubMed

    Dao, Jasmin M; McQuown, Susan C; Loughlin, Sandra E; Belluzzi, James D; Leslie, Frances M

    2011-06-01

    Epidemiological studies have shown that adolescent smoking is associated with health risk behaviors, including high-risk sexual activity and illicit drug use. Using rat as an animal model, we evaluated the behavioral and biochemical effects of a 4-day, low-dose nicotine pretreatment (60 μg/kg; intravenous) during adolescence and adulthood. Nicotine pretreatment significantly increased initial acquisition of cocaine self-administration, quinpirole-induced locomotor activity, and penile erection in adolescent rats, aged postnatal day (P)32. These effects were long lasting, remaining evident 10 days after the last nicotine treatment, and were observed when nicotine pretreatment was administered during early adolescence (P28-31), but not late adolescence (P38-41) or adulthood (P86-89). Neurochemical analyses of c-fos mRNA expression, and of monoamine transmitter and transporter levels, showed that forebrain limbic systems are continuing to develop during early adolescence, and that this maturation is critically altered by brief nicotine exposure. Nicotine selectively increased c-fos mRNA expression in the nucleus accumbens shell and basolateral amygdala in adolescent, but not adult animals, and altered serotonin markers in these regions as well as the prefrontal cortex. Nicotine enhancement of cocaine self-administration and quinpirole-induced locomotor activity was blocked by co-administration of WAY 100 635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide), a selective serotonin 1A (5-HT1A) receptor antagonist. Early adolescent pretreatment with the mixed autoreceptor/heteroceptor 5-HT1A receptor agonist, 8-OH-DPAT, but not the autoreceptor-selective agonist, S-15535, also enhanced quinpirole-induced locomotor activation. Nicotine enhancement of quinpirole-induced penile erection was not blocked by WAY 100 635 nor mimicked by 8-OH-DPAT. These findings indicate that early adolescent nicotine exposure uniquely alters limbic

  5. Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes

    PubMed Central

    ETTER, Jean-François; EISSENBERG, Thomas

    2016-01-01

    Objective To assess dependence levels in users of e-cigarettes, and compare them with dependence levels in users of nicotine gums and tobacco cigarettes. Design Self-reports from cross-sectional Internet and mail surveys. Comparisons of: a) 766 daily users of nicotine-containing e-cigarettes with 30 daily users of nicotine-free e-cigarettes; b) 911 former smokers who used the e-cigarette daily with 451 former smokers who used the nicotine gum daily (but no e-cigarette); c) 125 daily e-cigarette users who smoked daily (dual users) with two samples of daily smokers who did not use e-cigarettes (2206 enrolled on the Internet and 292 enrolled by mail from the general population of Geneva). We used the Fagerström Test for Nicotine Dependence, the Nicotine Dependence Syndrome Scale, the Cigarette Dependence Scale and versions of these scales adapted for e-cigarettes and nicotine gums. Results Dependence ratings were slightly higher in users of nicotine-containing e-cigarettes than in users of nicotine-free e-cigarettes. In former smokers, long-term (>3 months) users of e-cigarettes were less dependent on e-cigarettes than long-term users of the nicotine gum were dependent on the gum. There were few differences in dependence ratings between short-term (<=3 months) users of gums or e-cigarettes. Dependence on e-cigarettes was generally lower in dual users than dependence on tobacco cigarettes in the two other samples of daily smokers. Conclusions Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive. PMID:25561385

  6. 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

  7. 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. PMID:22583831

  8. 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

  9. 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

  10. An Investigation of Cigarettes Smoking Behavior and Nicotine Dependence among Chinese Methamphetamine Users in Two Provinces

    PubMed Central

    Wang, Ziyun; Bao, Yanping; Yan, Shiyan; Lian, Zhi; Jia, Zhenjun; Liu, Zhimin

    2014-01-01

    Objective. To survey cigarette behaviors and nicotine dependence among Chinese MA users, explore risk factors for high nicotine dependence, and analyze the relationship between nicotine dependence and MA-related euphoria and sexual impulse. Methods. A cross-sectional study, applying a self-designed questionnaire with the Fagerström Test for Nicotine Dependence (FTND) and Visual Analog Scale (VAS), was performed among 391 MA users in Beijing and Guangdong, China. Results. Most MA users were smokers, including 159 having high dependence on nicotine (HD users, FTND > 5) and 197 low or medium dependent (LMD users, FTND ≤ 5). Men or married users were more likely to be highly dependent than women or unmarried users. Higher MA dose and ever-use of ketamine or alcohol were associated with higher likelihood of high nicotine dependence. HD users reported significantly higher euphoria and stronger sexual impulse after using MA, indicated by higher VAS scores. Conclusions. Potential risk factors for high nicotine dependence among MA users may include male gender, being married, higher MA dosage, and ever-use of ketamine or alcohol, which should be taken into consideration in individualized health promotion on smoking cessation. Severe nicotine dependence was associated with stronger MA-related euphoria and sexual impulse and it should be confirmed by further studies. PMID:25025035

  11. 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

  12. Smoking habits and nicotine dependence of North Korean male defectors

    PubMed Central

    Kim, Sei Won; Lee, Jong Min; Ban, Woo Ho; Park, Chan Kwon; Yoon, Hyoung Kyu; Lee, Sang Haak

    2016-01-01

    Background/Aims: The smoking rates and patterns in the North Korean population are not well known. More than 20,000 North Korean defectors have settled in South Korea; thus, we can estimate the current North Korean smoking situation using this group. Methods: All North Korean defectors spend their first 3 months in a South Korean facility learning to adapt to their new home. We retrospectively analyzed the results from a questionnaire conducted among North Korean male defectors in this facility from August 2012 to February 2014. Results: Of 272 men, 84.2% were current smokers, 12.5% were ex-smokers, and 3.3% were non-smokers. The mean age of this group was 35.9 ± 11.3 years, and smoking initiation occurred at a mean age of 18.2 ± 4.7 years. Among the subjects, 78.1% had a family member who smoked. Of the 221 current smokers, 67.4% responded that they intended to quit smoking. Fagerström test and Kano test for social nicotine dependence (KTSND) results for current smokers were 3.35 ± 2.26 and 13.76 ± 4.87, respectively. Question 9 on the KTSND (doctors exaggerate the ill effects of smoking) earned a significantly higher score relative to the other questions and a significantly higher score in current smokers compared with non-smokers. Conclusions: The smoking rate in North Korean male defectors was higher than that indicated previously. However, interest in smoking cessation was high and nicotine dependence was less severe than expected. Further investigation is needed to identify an efficient method for North Korean smokers to stop smoking. PMID:26951917

  13. 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…

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

    PubMed Central

    Lewis, Alan S.; Qayyum, Zheala; Koslosky, Kourtney; Picciotto, Marina R.; Volkmar, Fred R.

    2016-01-01

    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 studies show nicotine administration can reduce aggression-related behaviors. Transdermal nicotine has been used to treat agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we report the use of transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently well tolerated, and reduced the need for emergency medication and restraint. These findings suggest further study of transdermal nicotine for aggression comorbid with ASD is warranted. PMID:25982311

  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. Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans

    PubMed Central

    Johnson, Eric O.; Breslau, Naomi; Hatsukami, Dorothy K.; Sadler, Brooke; Brooks, Andrew I.; Hesselbrock, Victor M.; Schuckit, Marc A.; Tischfield, Jay A.; Goate, Alison M.; Saccone, Nancy L.; Bierut, Laura J.

    2014-01-01

    Aims Studies have shown association between common variants in the α6–β3 nicotinic receptor subunit gene cluster and nicotine dependence in European Ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence, and whether this region contains additional genetic contributors to nicotine dependence. Design We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana, and cocaine dependence in three independent studies. Setting United States of America Participants European Americans and African Americans from three case control studies of substance dependence. Measurements Subjects were evaluated using the Semi-Structured Assessment for the Genetics of Alcoholism. Nicotine dependence was determined using the Fagerström Test for Nicotine Dependence. Findings rs13273442 was significantly associated to nicotine dependence across all three studies in both ancestry groups (OR=0.75, p=5.8 × 10−4 European Americans; OR=0.80, p=0.05 African Americans). No other substance dependence was consistently associated to this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442. Conclusions The common variant rs13273442 in the CHRNB3-CHNRA6 region is significantly associated to nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol, and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants likely account for some of the association of this region to nicotine dependence. PMID:24401102

  17. Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood

    PubMed Central

    Goriounova, Natalia A.; Mansvelder, Huibert D.

    2012-01-01

    The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs) are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings. PMID:22876231

  18. Trauma exposure, posttraumatic stress disorder and risk for alcohol, nicotine, and marijuana dependence in Israel

    PubMed Central

    Walsh, Kate; Elliott, Jennifer C.; Shmulewitz, Dvora; Aharonovich, Efrat; Strous, Rael; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah

    2014-01-01

    Background Substance dependence is more common among trauma-exposed individuals; however, most studies suggest that Posttraumatic Stress Disorder (PTSD) accounts for the link between trauma exposure (TE) and substance dependence. Objectives This study examined associations between TE and substance dependence (alcohol, nicotine, and marijuana), and whether PTSD accounted for this association. Method 1,317 Jewish Israeli household residents completed in-person structured interviews assessing TE, PTSD, and substance (alcohol, nicotine, marijuana) dependence between 2007–2009. Regression analyses examined associations among TE, PTSD, and substance dependence. Results In the full sample, mean number of traumatic events was 2.7 (sd=2.2), with 83.7% experiencing at least one event. In the full sample, mean number of PTSD symptoms was 2.5 (sd=3.4), with 13.5% meeting PTSD diagnostic criteria. Prevalence of alcohol dependence was 13.4%; nicotine dependence 52.8%; and marijuana dependence 12.1%. Number of traumatic events was associated with increased odds of alcohol (OR=1.3; 95% CI=1.2–1.4) and nicotine (OR=1.2; 95% CI=1.1–1.3) dependence. Similarly, any traumatic event exposure was associated with increased odds of alcohol (OR= 3.1; 95% CI= 1.6–6.0) and nicotine (OR=1.9; 95% CI=1.2–2.9) dependence. PTSD symptoms were associated with increased odds of alcohol (OR=1.2; 95% CI=1.1–1.3), nicotine (OR=1.1; 95% CI=1.1–1.2), and marijuana (OR=1.1; 95% CI=1.04–1.2) dependence; similarly, a PTSD diagnosis was associated with increased odds of alcohol (OR=3.4; 95% CI=2.1–5.5), nicotine (OR=2.2; 95% CI = 1.4–3.4), and marijuana (OR=2.6; 95% CI=1.2–5.9) dependence. PTSD symptoms accounted for a sizeable proportion of the TE effect on alcohol (46%) and nicotine dependence (31%). Conclusion Individuals with more traumatic events had heightened risk for alcohol and nicotine dependence, and PTSD symptoms partially accounted for this risk. However, marijuana

  19. Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: Findings from the COMMIT cohort

    PubMed Central

    Bousman, Chad A.; Rivard, Cheryl; Den Haese, Jason; Ambrosone, Christine; Hyland, Andrew

    2012-01-01

    Smoking many cigarettes per day (CPD) and short interval to first cigarette (TTF) after waking are two of the most heritable smoking phenotypes and comprise the Heavy Smoking Index (HSI). These phenotypes are often used as proxies for nicotine dependence (ND) and are associated with smoking cessation outcomes. Case-control and genome-wide association studies have reported links between single nucleotide polymorphisms (SNPs) in the alpha-5 and -3 nicotinic receptor subunit (CHRNA5 and CHRNA3) genes and CPD but few have examined TTF or cessation outcomes. In this study we longitudinally assessed 1301 European-American smokers at four time-points from 1988 to 2005. One CHRNA5 (rs16969968) and two CHRNA3 (rs1051703, rs6495308) SNPs were examined for their ability to predict smokers who ‘ever’ reported ND based on three phenotypic classifications: 1) 25+ CPD, 2) TTF < 10 minutes, and 3) HSI ≥ 4. In a subsample of 1157 quit attempters, we also examined each SNP’s ability to predict ‘ever’ quitting for a period of >6 months. Demographically adjusted logistic regressions showed significant allelic and genotypic associations between all three SNPs and CPD but not TTF, HSI, or smoking cessation. Carriers of both the rs16969968-AA and rs6495308-TT genotypes had approximately two-fold greater odds for ND defined using CPD or TTF. Results suggest nicotinic receptor variants are associated with greater odds of ND according to CPD and to a lesser extent TTF. Research examining the effect of nicotinic receptor genetic variation on ND phenotypes beyond CPD is warranted. PMID:22223462

  20. 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

  1. Nicotine dependence and psychosis in Bipolar disorder and Schizoaffective disorder, Bipolar type.

    PubMed

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

    2016-06-01

    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. 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 = 1544). Participants were classified with or without nicotine dependence. Diagnostic groups were compared to controls (N = 10065) using logistic regression. 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). Bipolar disorder patients experiencing more severity of psychosis have more risk of nicotine dependence. © 2015 Wiley Periodicals, Inc. PMID:26467098

  2. 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

  3. Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal

    PubMed Central

    Natividad, Luis A.; Buczynski, Matthew W.; Parsons, Loren H.; Torres, Oscar; O'Dell, Laura E.

    2012-01-01

    Adolescent smokers report enhanced positive responses to tobacco and fewer negative effects of withdrawal from this drug than adults, and this is believed to propel higher tobacco use during adolescence. Differential dopaminergic responses to nicotine are thought to underlie these age-related effects, since adolescent rats experience lower withdrawal-related deficits in nucleus accumbens (NAcc) dopamine versus adults. This study examined whether age differences in NAcc dopamine during withdrawal are mediated by excitatory or inhibitory transmission in the ventral tegmental area (VTA) dopamine cell body region. In vivo microdialysis was used to monitor extracellular levels of glutamate and gamma-aminobutyric acid (GABA) in the VTA of adolescent and adult rats experiencing nicotine withdrawal. In adults, nicotine withdrawal produced decreases in VTA glutamate levels (44% decrease) and increases in VTA GABA levels (38% increase). In contrast, adolescents did not exhibit changes in either of these measures. Naïve controls of both ages did not display changes in NAcc dopamine, VTA glutamate or VTA GABA following mecamylamine. These results indicate that adolescents display resistance to withdrawal-related neurochemical processes that inhibit mesolimbic dopamine function in adults experiencing nicotine withdrawal. Our findings provide a potential mechanism involving VTA amino acid neurotransmission that modulates age differences during withdrawal. PMID:22905672

  4. Immunochromatographic Assessment of Salivary Cotinine and Its Correlation With Nicotine Dependence in Tobacco Chewers

    PubMed Central

    Asha, V; Dhanya, M

    2015-01-01

    Background: This study assessed the correlation between nicotine dependence and salivary cotinine levels in tobacco chewers and checked the reliability of Fagerstorm test in tobacco cessation programmes. Methods: The study sample included 75 tobacco chewers aged between 20 to 50 years. Self-reported nicotine dependence was evaluated using Fagerstorm Test for Nicotine dependence-smokeless tobacco questionnaire. Patients were categorized into low, moderate and high dependent chewers based on their answers to the questionnaire. The unstimulated salivary cotinine levels were measured by immunochromatographic assay using the NicAlert saliva test. Data was analysed using the chi-square test for testing intra-group variation, analysis of variance for testing between-groups variation, and the Spearman coefficient for assessing the association between variables. Results: No statistically significant association was seen between salivary cotinine levels and nicotine dependence. A weak positive correlation was noted between the above variables (r = 0.230). In the group studied, it was evident that the patients were under-reporting the nicotine dependence. Conclusions: The measurement of salivary cotinine by immunochromatographic assay using NicAlert saliva test is a useful and convenient method for studying the nicotine dependence in tobacco chewers. Immunochromatography-based cotinine test strips are an easy method of detecting salivary cotinine in a dental setup. From this study we are of the opinion that a simple questionnaire like Fagerstorm test can give a less adequate analysis of patient’s dependence especially in countries like India, where patients tend to under-report their dependency. Immediate feedback from a chairside test can help both the dentists and patients during a tobacco cessation programme. PMID:26151050

  5. Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice.

    PubMed

    Bagdas, Deniz; Muldoon, Pretal P; Zhu, Andy Z X; Tyndale, Rachel F; Damaj, M Imad

    2014-10-01

    Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the principal pathway by which active nicotine is removed from circulation. We therefore hypothesized that inhibition of mouse CYP2A5, the ortolog of human CYP2A6, by methoxsalen (8-methoxypsoralen) alter dependence-related behaviors of nicotine in the mouse. Conditioned place preference (CPP) test was used to assess the appetitive reward-like properties and precipitated nicotine withdrawal to assess physical (somatic and hyperalgesia) and affective (anxiety-related behaviors) measures. The nicotine plasma levels were also measured with or without methoxsalen pretreatment. Methoxsalen (15 and 30 mg/kg, intraperitoneally) pretreatment enhanced nicotine-induced preference in mice (p<0.05). However, there was a lack of enhancement of nicotine in the CPP test after the highest dose of the CYP-2A5 inhibitor. Similarly to the CPP results, repeated administration of methoxsalen increased the intensity of mecamylamine-precipitated withdrawal signs. The potentiation of nicotine preference and withdrawal intensity by methoxsalen was accompanied by significant increase in nicotine plasma levels in mice (p<0.05). Finally, methoxsalen enhanced the ability of a very low dose of nicotine (0.05 mg/kg) to reverse withdrawal signs in mice undergoing spontaneous withdrawal after chronic nicotine infusion (p<0.05). In conclusion, inhibition of nicotine metabolism by methoxsalen alters the behavioral effects of nicotine in the mouse. Combining CYP2A6 inhibitors with low dose nicotine replacement therapies may have a beneficial role in smoking cessation because it will decrease the drug elimination rate and maintain plasma and brain nicotine levels. PMID:24859605

  6. Gutkha Addiction: Nicotine Dependence or a Conditioned Reflex?

    PubMed Central

    Joshi, Prathamesh Satish; Prashant, M C; Nagpal, Neelu; Patil, Atulkumar A; Ahuja, Rinky; Mathur, Vidhi

    2015-01-01

    Background: A pre-packaged mixture of areca nut, tobacco, slaked lime, catechu, and flavoring agents is popularly known as Gutkha. Aim of study is to analyze the addiction biology of Gutkha chewing and to assess efficacy of a cessation program based on nicotine replacement therapy (NRT). Materials and Methods: Patterns of addiction of 400 Gutkha chewers were analyzed with a questionnaire-based survey. Urine cotinine levels of 60 subjects undergoing NRT were periodically estimated using gas chromatography. Results: Mean urine cotinine levels of relapse and relapse-free cases were 5800.38 µg/g of creatine and 5622.16 µg/g of creatine. The difference was not found to be statistically significant. A 83.3% of the subjects associated their chewing habit with day to day activities. Overall relapse rate was found to be 79%. The most common reported reason for relapse was unacceptable taste and form of nicotine chewing gums. Conclusion: Repetitive coexistence in time of an indifferent act and the act of chewing Gutkha where, the act of chewing is almost always preceded by the indifferent act sets in a conditioned reflex. Gutkha addiction can be considered as a form of conditioned reflex, rather than actual craving for nicotine. PMID:26668480

  7. 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

  8. 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

  9. 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

  10. [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

  11. Nicotine Stimulates Nerve Growth Factor in Lung Fibroblasts through an NFκB-Dependent Mechanism

    PubMed Central

    Wongtrakool, Cherry; Grooms, Kora; Bijli, Kaiser M.; Crothers, Kristina; Fitzpatrick, Anne M.; Hart, C. Michael

    2014-01-01

    Rationale Airway hyperresponsiveness (AHR) is classically found in asthma, and persistent AHR is associated with poor asthma control. Although airway smooth muscle (ASM) cells play a critical pathophysiologic role in AHR, the paracrine contributions of surrounding cells such as fibroblasts to the contractile phenotype of ASM cells have not been examined fully. This study addresses the hypothesis that nicotine promotes a contractile ASM cell phenotype by stimulating fibroblasts to increase nerve growth factor (NGF) secretion into the environment. Methods Primary lung fibroblasts isolated from wild type and α7 nicotinic acetylcholine receptor (α7 nAChR) deficient mice were treated with nicotine (50 µg/ml) in vitro for 72 hours. NGF levels were measured in culture media and in bronchoalveolar lavage (BAL) fluid from asthmatic, smoking and non-smoking subjects by ELISA. The role of the NFκB pathway in nicotine-induced NGF expression was investigated by measuring NFκB nuclear translocation, transcriptional activity, chromatin immunoprecipitation assays, and si-p65 NFκB knockdown. The ability of nicotine to stimulate a fibroblast-mediated, contractile ASM cell phenotype was confirmed by examining expression of contractile proteins in ASM cells cultured with fibroblast-conditioned media or BAL fluid. Results NGF levels were elevated in the bronchoalveolar lavage fluid of nicotine-exposed mice, current smokers, and asthmatic children. Nicotine increased NGF secretion in lung fibroblasts in vitro in a dose-dependent manner and stimulated NFκB nuclear translocation, p65 binding to the NGF promoter, and NFκB transcriptional activity. These responses were attenuated in α7 nAChR deficient fibroblasts and in wild type fibroblasts following NFκB inhibition. Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells. Conclusion Nicotine stimulates NGF release by lung fibroblasts through α7 nAChR and NFκB dependent pathways

  12. 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…

  13. 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. PMID:27435419

  14. Effect of Neuronal Nicotinic Acetylcholine Receptor Genes (CHRN) on Longitudinal Cigarettes per Day in Adolescents and Young Adults

    PubMed Central

    2014-01-01

    Introduction: Few studies have sought to identify specific genetic markers associated with cigarettes per day (CPD) during adolescence and young adulthood, the period of greatest vulnerability for the development of nicotine dependence. Methods: We used a longitudinal design to investigate the effect of neuronal nicotinic acetylcholine receptor (CHRN) subunit genes on CPD from 15 to 21 years of age in young smokers of European descent (N = 439, 59% female). The number of CPD typically smoked during the previous 30 days was self-reported. Single nucleotide polymorphisms (SNPs) from CHRN genes were genotyped using DNA extracted from saliva samples collected at the 5-year assessment. Mixed-model analyses of SNP effects were computed across age at the time of assessment using log-transformed CPD as the phenotype. Data from the 1000 Genomes Project were used to clarify the architecture of CHRN genes to inform SNP selection and interpretation of results. Results: CPD was associated with a CHRNB3A6 region tagged by rs2304297, with CHRNA5A3B4 haplotype C (tagged by rs569207), and with the CHRNA2 SNP rs2271920, ps < .004. The reliability of single-SNP associations was supported by the correspondence between a more extensive set of SNP signals and the underlying genetic architecture. The 3 signals identified in this study appear to make independent contributions to CPD, and their combined effect accounts for 5.5% of the variance in log-transformed CPD. Conclusions: Level of CPD during adolescence and young adulthood is associated with CHRNB3A6, CHRNA5A3B4, and CHRNA2. PMID:23943838

  15. 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

  16. 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. PMID:17720206

  17. Everyday Discrimination Is Associated With Nicotine Dependence Among African American, Latino, and White Smokers

    PubMed Central

    2014-01-01

    Introduction: Discrimination is a commonly perceived stressor among African Americans and Latinos, and previous research has linked stress with substance dependence. Although studies have shown a link between discrimination and smoking, little is known about the relationship between discrimination and nicotine dependence. Methods: A total of 2,376 African American (33.4%; n = 794), Latino (33.1%; n = 786), and White (33.5%; n = 796) smokers completed an online survey. Everyday discrimination experiences were described in total and by race/ethnicity. Covariate-adjusted linear regression analyses were conducted to evaluate the associations between everyday discrimination and indicators of nicotine dependence. Results: Most participants (79.1%), regardless of race/ethnicity, reported experiencing everyday discrimination. However, total scores on the discrimination measure were higher among Latinos and African Americans than among Whites (p < .001). Race/ethnicity/national origin was the most commonly perceived reason for everyday discrimination among African Americans and Latinos, whereas physical appearance was the most commonly perceived reason among Whites. Regression analyses indicated that everyday discrimination was positively associated with indicators of nicotine dependence, including the Heaviness of Smoking Index (HSI; p < .001) and the Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM) scales (all ps < .001). There was a significant interaction between race/ethnicity and discrimination, such that discrimination was associated with the HSI only among Latinos. Similarly, discrimination was most strongly associated with the WISDM scales among Latinos. Conclusions: Analyses indicated that discrimination is a common stressor associated with nicotine dependence. Findings suggest that greater nicotine dependence is a potential pathway through which discrimination may influence health. PMID:24302634

  18. 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…

  19. 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.

  20. 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…

  1. 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.

  2. 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

  3. 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. PMID:23233221

  4. 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

  5. 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

  6. 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

  7. Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine self-administration during adulthood in male C57BL/6J mice.

    PubMed

    Dickson, Price E; Miller, Mellessa M; Rogers, Tiffany D; Blaha, Charles D; Mittleman, Guy

    2014-01-01

    Studies of adolescent drug use show (1) a pattern in which the use of tobacco precedes the use of other drugs and (2) a positive relationship between adolescent tobacco use and later drug use. These observations have led to the hypothesis that a causal relationship exists between early exposure to nicotine and the later use of hard drugs such as cocaine. Using male C57BL/6J mice, we tested the hypothesis that nicotine exposure in adolescence leads to increased intravenous self-administration (IVSA) of cocaine in adulthood. Using miniature osmotic pumps, we exposed mice and their littermate controls to nicotine (24 mg/kg/day) or vehicle, respectively, over the entire course of adolescence [postnatal days (P) 28-56]. Nicotine exposure was terminated on P56 and mice were not exposed to nicotine again during the experiment. On P73, mice were allowed to acquire cocaine IVSA (1.0 mg/kg/infusion) and a dose-response curve was generated (0.18, 0.32, 0.56, 1.0, 1.8 mg/kg/infusion). Lever pressing during extinction conditions was also evaluated. All mice rapidly learned to lever press for the combination of cocaine infusions and non-drug stimuli. Analysis of the dose-response curve revealed that adolescent nicotine-exposed mice self-administered significantly more (P < 0.05) cocaine than controls at all but the highest dose. No significant differences were observed between adolescent nicotine-exposed and control mice during the acquisition or extinction stages. These results indicate that adolescent nicotine exposure can increase cocaine IVSA in mice, which suggests the possibility of a causal link between adolescent tobacco use and later cocaine use in humans. PMID:22978678

  8. Chemical dependency and adolescent self-esteem.

    PubMed

    Wasson, D; Anderson, M A

    1995-08-01

    The purpose of this descriptive study is to determine whether self-esteem differs between chemically dependent adolescents and adolescents from the general high school population. The Self-Esteem Inventory (Coopersmith, 1987) was completed by 119 adolescents (31 inpatient, 31 aftercare, and 57 general high school students) aged 13 to 18. Findings suggest that inpatient, chemically dependent adolescents have lower self-esteem than the other two groups. For the chemically dependent adolescent, nursing case management with communication among and between health care providers, school professionals, and family may facilitate successful, long-term recovery. For adolescents at risk for development of chemical dependence, nursing health promotion behaviors, such as early assessment and implementation of self-esteem-building activities, may assist in prevention of chemical dependency. PMID:7633338

  9. 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

  10. 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. PMID:24647948

  11. Dopamine genes and nicotine dependence in treatment seeking and community smokers

    PubMed Central

    Bergen, Andrew W.; Conti, David V.; Berg, David Van Den; Lee, Wonho; Liu, Jinghua; Li, Dalin; Guo, Nan; Mi, Huaiyu; Thomas, Paul D.; Lessov-Schlaggar, Christina N.; Krasnow, Ruth; He, Yungang; Nishita, Denise; Jiang, Ruhong; McClure, Jennifer B.; Tildesley, Elizabeth; Hops, Hyman; Tyndale, Rachel F.; Benowitz, Neal L.; Lerman, Caryn; Swan, Gary E.

    2013-01-01

    We utilized a cohort of 828 treatment seeking self-identified white cigarette smokers (50% female) to rank candidate gene single nucleotide polymorphisms (SNPs) associated with the Fagerström Test for Nicotine Dependence (FTND), a measure of nicotine dependence which assesses quantity of cigarettes smoked and time- and place-dependent characteristics of the respondent’s smoking behavior. 1123 SNPs at 55 autosomal candidate genes, nicotinic acetylcholine receptors and genes involved in dopaminergic function, were tested for association to baseline FTND scores adjusted for age, depression, education, sex and study site. SNP P values were adjusted for the number of transmission models, the number of SNPs tested per candidate gene, and their intragenic correlation. DRD2, SLC6A3 and NR4A2 SNPs with adjusted P values < 0.10 were considered sufficiently noteworthy to justify further genetic, bioinformatic and literature analyses. Each independent signal among the top-ranked SNPs accounted for ~1% of the FTND variance in this sample. The DRD2 SNP appears to represent a novel association with nicotine dependence. The SLC6A3 SNPs have previously been shown to be associated with SLC6A3 transcription or dopamine transporter density in vitro, in vivo and ex vivo. Analysis of SLC6A3 and NR4A2 SNPs identified a statistically significant gene-gene interaction (P=0.001), consistent with in vitro evidence that the NR4A2 protein product (NURR1) regulates SLC6A3 transcription. A community cohort of N=175 multiplex ever smoking pedigrees (N=423 ever smokers) provided nominal evidence for association with the FTND at these top ranked SNPs, uncorrected for multiple comparisons. PMID:19494806

  12. 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

  13. 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

  14. 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. PMID:24084318

  15. Bruxism Is Associated With Nicotine Dependence: A Nationwide Finnish Twin Cohort Study

    PubMed Central

    Ahlberg, J.; Hublin, C.; Broms, U.; Madden, P. A. F.; Könönen, M.; Koskenvuo, M.; Lobbezoo, F.; Kaprio, J.

    2010-01-01

    Objectives: To investigate the association of smoking with bruxism while controlling for genetic and environmental factors using a co-twin-control design. Especially, the role of nicotine dependence was studied in this context. Methods: The material derives from the Finnish Twin Cohort consisting of 12,502 twin individuals who responded to a questionnaire in 1990 (response rate of 77%). All were born in 1930–1957, the mean age being 44 years. The questionnaire covered 103 multiple choice questions, 7 dealing with tobacco use and 22 with sleep and vigilance matters, including perceived bruxism. In addition, a subsample derived from the Nicotine Addiction Genetics Finland Study containing 445 twin individuals was studied. Results: In age- and gender-controlled multinomial logistic regression, both monthly and rarely reported bruxism associated with both current cigarette smoking (odds ratio [OR] = 1.74 and 1.64) and former cigarette smoking (OR = 1.64 and 1.47). Weekly bruxism associated with current smoking (OR = 2.85). Current smokers smoking 20 or more cigarettes a day reported weekly bruxism more likely (OR = 1.61–1.97) than those smoking less. Among twin pairs (N = 142) in which one twin was a weekly bruxer and the cotwin a never bruxer, there were 13 monozygotic pairs in which one twin was a current smoker and the other twin was not. In all cases, the bruxer was the smoker (p = .0003). Nicotine dependence associated significantly with bruxism. Conclusions: Our twin study provides novel evidence for a possible causal link between tobacco use and bruxism among middle-aged adults. Nicotine dependence may be a significant predisposing factor for bruxism. PMID:21041838

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

    PubMed

    Isomura, Takeshi; Suzuki, Joji; Murai, Toshiya

    2014-04-01

    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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23591971

  18. 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

    2013-01-01

    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. PMID:23591971

  19. 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

  20. Sex differences in resting state brain function of cigarette smokers and links to nicotine dependence.

    PubMed

    Beltz, Adriene M; Berenbaum, Sheri A; Wilson, Stephen J

    2015-08-01

    Sex--a marker of biological and social individual differences--matters for drug use, particularly for cigarette smoking, which is the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task, is important for understanding cigarette smoking, as it has been shown to differentiate between smokers and nonsmokers. But, it is unclear whether and how sex influences the link between resting state brain function and smoking behavior. In this study, the authors demonstrate that sex is indeed associated with resting state connectivity in cigarette smokers, and that sex moderates the link between resting state connectivity and self-reported nicotine dependence. Using functional MRI and behavioral data from 50 adult daily smokers (23 women), the authors found that women had greater connectivity than men within the default mode network, and that increased connectivity within the reward network was related to increased nicotine tolerance in women but to decreased nicotine tolerance in men. Findings highlight the importance of sex-related individual differences reflected in resting state connectivity for understanding the etiology and treatment of substance use problems. PMID:26237322

  1. 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. PMID:25907750

  2. 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…

  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. Investigating the Relationship between Personality Traits and Self-Control and Nicotine Dependence Symptoms in Male Prisoners in Kerman, Iran

    PubMed Central

    Baniassadi, Tayebeh; Javanmard, Zeinab; Zivari-Rahman, Mahmoud; Shokouhi-Moqhaddam, Solmaz; Adhami, Masoumeh

    2015-01-01

    Background Smoking is the most common and cheapest addictive substance and has physical, psychological, and social side effects. Personality traits and low self-control have been identified as key factors for substance and tobacco abuse. This study examined the relationship between personality traits and self-control, and symptoms of nicotine dependence in male prisoners. Methods This was a descriptive correlational study. The research sample consisted of 384 male prisoners in Kerman, Iran. The participants were selected using simple random sampling method. The data collection tools consisted of the NEO five factor personality inventory (NEO-FFI), self-control Inventory, and the nicotine dependence symptoms inventory. Findings The mean age of the prisoners was 35.33 ± 9.28 year. The results showed a significant negative relationship between self-control and nicotine dependence. The most important predictors of prisoners’ self-control were the personality traits of conscientiousness, neuroticism, openness, and temperamental neuroticism, respectively. The most important predictors of nicotine dependence in prisons were personality traits of adaptability, temperamental neuroticism, extroversion, and openness, respectively. Conclusion Personality traits and self-control have an important role in nicotine dependence; therefore, by training self-control, behaviors such as smoking and consumption of drugs can be reduced. PMID:26322215

  5. 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

  6. 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

  7. 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

  8. 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

  9. The Contribution of Rare and Common Variants in 30 Genes to Risk Nicotine Dependence

    PubMed Central

    Yang, Jiekun; Wang, Shaolin; Yang, Zhongli; Hodgkinson, Colin A.; Iarikova, Polina; Ma, Jennie Z.; Payne, Thomas J.; Goldman, David; Li, Ming D.

    2014-01-01

    Genetic and functional studies have revealed that both common and rare variants of several nicotinic acetylcholine receptor (nAChR) 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 (MSTF) 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 Nicotine Dependence (FTND) scores, or indexed cigarettes per day (CPD) 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 106 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

  10. Oxidative stress and inflammatory markers are associated with depression and nicotine dependence.

    PubMed

    Vargas, Heber Odebrecht; Nunes, Sandra Odebrecht Vargas; de Castro, Márcia Regina Pizzo; Vargas, Mateus Mendonça; Barbosa, Décio Sabbatini; Bortolasci, Chiara Cristina; Venugopal, Kamalesh; Dodd, Seetal; Berk, Michael

    2013-06-01

    To determine if oxidative stress and inflammation are linked with major depressive disorder, nicotine dependence and both disorders combined. This study comprised 150 smokers and 191 never smokers. The instruments were: a socio-demographic questionnaire, diagnoses of mood disorder and nicotine dependence according to DSM-IV, (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Laboratory assessments included: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde (MDA), total reactive antioxidant potential (TRAP), advanced oxidation protein products (AOPP), fibrinogen concentrations, homocysteine, erythrocytes sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were assayed from blood specimens. Statistically significant differences were found among depressed smokers who had more severe depressive symptoms, a higher risk of alcohol consumption, more suicide attempts, and more disability for work than non-depressed never smokers. Depressed smokers had significantly higher levels of NOx, fibrinogen, hs-CRP, AOPP, ESR and lower levels of TRAP compared to non-depressed never smokers. Depressed smokers had significant levels of oxidative stress and inflammatory biomarkers after adjusting for gender, age, years of education, disability for work, and laboratory measures. The levels of NOx, lipid hydroperoxides, AOPP, and fibrinogen were substantially higher, whereas levels of TRAP were lower in depressed smokers compared to non-depressed never smokers. (1) Depressed smokers exhibited altered concentrations of NOx, lipid hydroperoxides, AOPP, TRAP, and fibrinogen. (2) Depressed smokers were more unable to work, showed more severe depressive symptoms and attempted suicide more frequently. PMID:23583694

  11. 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

  12. 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

  13. 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

  14. 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. PMID:24616009

  15. 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

  16. Resequencing of Nicotinic Acetylcholine Receptor Genes and Association of Common and Rare Variants with the Fagerström Test for Nicotine Dependence

    PubMed Central

    Wessel, Jennifer; McDonald, Sarah M; Hinds, David A; Stokowski, Renee P; Javitz, Harold S; Kennemer, Michael; Krasnow, Ruth; Dirks, William; Hardin, Jill; Pitts, Steven J; Michel, Martha; Jack, Lisa; Ballinger, Dennis G; McClure, Jennifer B; Swan, Gary E; Bergen, Andrew W

    2010-01-01

    Common single-nucleotide polymorphisms (SNPs) at nicotinic acetylcholine receptor (nAChR) subunit genes have previously been associated with measures of nicotine dependence. We investigated the contribution of common SNPs and rare single-nucleotide variants (SNVs) in nAChR genes to Fagerström test for nicotine dependence (FTND) scores in treatment-seeking smokers. Exons of 10 genes were resequenced with next-generation sequencing technology in 448 European-American participants of a smoking cessation trial, and CHRNB2 and CHRNA4 were resequenced by Sanger technology to improve sequence coverage. A total of 214 SNP/SNVs were identified, of which 19.2% were excluded from analyses because of reduced completion rate, 73.9% had minor allele frequencies <5%, and 48.1% were novel relative to dbSNP build 129. We tested associations of 173 SNP/SNVs with the FTND score using data obtained from 430 individuals (18 were excluded because of reduced completion rate) using linear regression for common, the cohort allelic sum test and the weighted sum statistic for rare, and the multivariate distance matrix regression method for both common and rare SNP/SNVs. Association testing with common SNPs with adjustment for correlated tests within each gene identified a significant association with two CHRNB2 SNPs, eg, the minor allele of rs2072660 increased the mean FTND score by 0.6 Units (P=0.01). We observed a significant evidence for association with the FTND score of common and rare SNP/SNVs at CHRNA5 and CHRNB2, and of rare SNVs at CHRNA4. Both common and/or rare SNP/SNVs from multiple nAChR subunit genes are associated with the FTND score in this sample of treatment-seeking smokers. PMID:20736995

  17. 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

  18. 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

  19. Extended access to nicotine leads to a CRF1 receptor dependent increase in anxiety-like behavior and hyperalgesia in rats

    PubMed Central

    Cohen, Ami; Treweek, Jennifer; Edwards, Scott; Leão, Rodrigo Molini; Schulteis, Gery; Koob, George F.; George, Olivier

    2013-01-01

    Background Tobacco dependence is associated with the emergence of negative emotional states during withdrawal, including anxiety and nociceptive hypersensitivity. However, the current animal models of nicotine dependence have focused on the mechanisms that mediate the acute reinforcing effects of nicotine and failed to link increased anxiety and pain during abstinence with excessive nicotine self-administration. Here, we tested the hypothesis that the activation of corticotropin-releasing factor-1 (CRF1) receptors and emergence of the affective and motivational effects of nicotine abstinence only occur in rats with long access (> 21 h/day, LgA) and not short (1 h/day, ShA) access to nicotine self-administration. Methods ShA and LgA rats were tested for anxiety-like behavior, nociceptive thresholds, somatic signs of withdrawal, and nicotine intake after 3 days of abstinence. The role of CRF1 receptors during abstinence was tested using systemic or intracerebral infusion of MPZP, a CRF1 receptor antagonist, in the central nucleus of the amygdala (CeA). Results LgA but not ShA rats exhibited abstinence-induced increases in anxiety-like behavior and nociceptive hypersensitivity, which both predicted subsequent excessive nicotine intake and were prevented by systemic administration of MPZP. Intra-CeA MPZP infusion prevented abstinence-induced increases in nicotine intake and nociceptive hypersensitivity. Conclusions These findings demonstrate that the model of short access to nicotine self-administration has limited validity for tobacco dependence, highlight the translational relevance of the model of extended-intermittent access to nicotine self-administration for tobacco dependence, and demonstrate that activation of CRF1 receptors is required for the emergence of abstinence-induced anxiety-like behavior, hyperalgesia, and excessive nicotine intake. PMID:23869743

  20. 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

  1. 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

  2. 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

  3. 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

  4. cGMP/cGMP-dependent protein kinase pathway modulates nicotine-induced currents through the activation of α-bungarotoxin-insensitive nicotinic acetylcholine receptors from insect neurosecretory cells.

    PubMed

    Mannai, Safa; Bitri, Lofti; Thany, Steeve H

    2016-06-01

    Insect neurosecretory cells, called dorsal unpaired median neurons, are known to express two α-bungarotoxin-insensitive nicotinic acetylcholine receptor (nAChR) subtypes, nAChR1 and nAChR2. It was demonstrated that nAChR1 was sensitive to cAMP/cAMP-dependent protein kinase (PKA) regulation, resulting in a modulation of nicotine currents. In this study, we show that cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway modulates nicotine-induced currents, as increased cGMP affects the second compound of the biphasic current-voltage curve, corresponding to the nAChR2 receptors. Indeed, maintaining the guanosine triphosphate level with 100 μM guanosine triphosphate-γ-S increased nicotine currents through nAChR2. We also demonstrated that inhibition of PKG activity with 0.2 μM (8R,9S,11S)-(-)-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-trizadibenzo-(a,g)-cycloocta-(c,d,e)-trinden-1-one (KT5823), a PKG specific inhibitor, reduced nicotine-induced current amplitudes. KT5823 effect on nicotine currents is associated with calcium (Ca(2+) ) activity because inhibition of Ca(2+) concentration with cadmium chloride (CdCl2 ) abolished KT5823-induced inhibition mediated by nAChR2. However, specific inhibition of nitric oxide-guanylyl cyclase (GC) complex by 10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly increased nicotine-induced current amplitudes on both nAChR1 and nAChR2. These results suggest that nicotine-induced currents mediated by both α-bungarotoxin-insensitive nAChR1 and nAChR2 are coupled to the cGMP/PKG pathway. We propose that nicotinic acetylcholine receptor activation induces an increase in intracellular calcium (Ca(2+) ) concentration. Elevation of intracellular Ca(2+) results in the formation of Ca(2+) -calmodulin (CaM) complex, which activates guanylyl cyclase (GC) and/or adenylyl cyclase (AC). Ca(2+) -CaM complex could activate Ca(2+) calmodulin kinase II which

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

    PubMed

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

    2015-10-01

    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

  6. 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

  7. Smoking History, Nicotine Dependence, and Changes in Craving and Mood during Short-Term Smoking Abstinence in Alcohol Dependent vs. Control Smokers

    PubMed Central

    Heffner, Jaimee L.; Mingione, Carolyn; Blom, Thomas J.; Anthenelli, Robert M.

    2010-01-01

    Objective The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers. Method AD (n=119) and control (n=55) ever smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N=34) and control (N=19) participants during a six-hour period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B). Results Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 minutes of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS. Conclusions Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD. PMID:21106299

  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. CHRNB3 is more strongly associated with FTCD-based nicotine dependence than cigarettes per day: phenotype definition changes GWAS results

    PubMed Central

    Rice, John P.; Hartz, Sarah; Agrawal, Arpana; Almasy, Laura; Bennett, Siiri; Breslau, Naomi; Bucholz, Kathleen K.; Doheny, Kimberly F.; Edenberg, Howard J.; Goate, Alison M.; Hesselbrock, Victor; Howells, William B.; Johnson, Eric O.; Kramer, John; Krueger, Robert F.; Kuperman, Samuel; Laurie, Cathy; Manolio, Teri A.; Neuman, Rosalind J.; Nurnberger, John I.; Porjesz, Bernice; Pugh, Elizabeth; Ramos, Erin M.; Saccone, Nancy; Saccone, Scott; Schuckit, Marc; Bierut, Laura J.

    2012-01-01

    Aims Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerström Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. Design Genome-wide association study Setting Community sample Participants A total of 3,365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2,267 were European Americans,999 were African Americans. Measurements Nicotine dependence defined by FTCD score ≥4, CPD Findings The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 (OR=0.65, p=2.4×10−8). This association was further strengthened in a meta-analysis with a previously published dataset (combined p=6.7 ×10−16, total n=4,200).When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β=−0.08, p=0.0007). Conclusions Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence (FTCD) show different associations with polymorphisms in genetic loci. PMID:22524403

  10. Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence

    PubMed Central

    Pizzo de Castro, Márcia Regina; Ehara Watanabe, Maria Angelica; Losi Guembarovski, Roberta; Odebrecht Vargas, Heber; Vissoci Reiche, Edna Maria; Kaminami Morimoto, Helena; Dodd, Seetal; Berk, Michael

    2014-01-01

    Background Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. Materials and methods Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. Results Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05–4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24–9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95–23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23–129.91, P<0.006). Conclusion This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress. PMID:24637631

  11. 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

  12. Tobacco Retailer Proximity and Density and Nicotine Dependence Among Smokers With Serious Mental Illness

    PubMed Central

    Young-Wolff, Kelly C.; Henriksen, Lisa; Delucchi, Kevin

    2014-01-01

    Objectives. We examined the density and proximity of tobacco retailers and associations with smoking behavior and mental health in a diverse sample of 1061 smokers with serious mental illness (SMI) residing in the San Francisco Bay Area of California. Methods. Participants’ addresses were geocoded and linked with retailer licensing data to determine the distance between participants’ residence and the nearest retailer (proximity) and the number of retailers within 500-meter and 1-kilometer service areas (density). Results. More than half of the sample lived within 250 meters of a tobacco retailer. A median of 3 retailers were within 500 meters of participants’ residences, and a median of 12 were within 1 kilometer. Among smokers with SMI, tobacco retailer densities were 2-fold greater than for the general population and were associated with poorer mental health, greater nicotine dependence, and lower self-efficacy for quitting. Conclusions. Our findings provide further evidence of the tobacco retail environment as a potential vector contributing to tobacco-related disparities among individuals with SMI and suggest that this group may benefit from progressive environmental protections that restrict tobacco retail licenses and reduce aggressive point-of-sale marketing. PMID:24922145

  13. 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

  14. Comparison of Nicotine Dependence Indicators in Predicting Quitting among Pregnant Smokers

    PubMed Central

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

    2015-01-01

    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 to cigarettes per day (CPD) and the Heaviness of Smoking Index (HSI) in predicting late-pregnancy abstinence among 289 pregnant women enrolled in four 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 three 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 entered first (c = 0.67), then CPD (c = 0.77), quit attempts pre-pregnancy (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

  15. 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

  16. Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

    PubMed

    Olfson, E; Saccone, N L; Johnson, E O; Chen, L-S; Culverhouse, R; Doheny, K; Foltz, S M; Fox, L; Gogarten, S M; Hartz, S; Hetrick, K; Laurie, C C; Marosy, B; Amin, N; Arnett, D; Barr, R G; Bartz, T M; Bertelsen, S; Borecki, I B; Brown, M R; Chasman, D I; van Duijn, C M; Feitosa, M F; Fox, E R; Franceschini, N; Franco, O H; Grove, M L; Guo, X; Hofman, A; Kardia, S L R; Morrison, A C; Musani, S K; Psaty, B M; Rao, D C; Reiner, A P; Rice, K; Ridker, P M; Rose, L M; Schick, U M; Schwander, K; Uitterlinden, A G; Vojinovic, D; Wang, J-C; Ware, E B; Wilson, G; Yao, J; Zhao, W; Breslau, N; Hatsukami, D; Stitzel, J A; Rice, J; Goate, A; Bierut, L J

    2016-05-01

    The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer. PMID:26239294

  17. An examination of the Fagerström Test for Nicotine Dependence among concurrent tobacco and khat users.

    PubMed

    Nakajima, Motohiro; al'Absi, Mustafa; Dokam, Anisa; Alsoofi, Mohammed; Khalil, Najat Sayem

    2012-01-01

    The current study examined the psychometric properties of the Fagerström Test for Nicotine Dependence (FTND) among tobacco smokers who use khat (Catha edulis), a widely used substance in East Africa and Arabian Peninsula. We also explored gender differences in response to FTND items because little attention has been paid to women's smoking behavior in Middle Eastern societies. A total of 103 (38 women) concurrent users (mean age +/- SD: 24.4 +/- 5.2) were recruited from two universities in Yemen. An Arabic version of FTND was developed using back-translation method. Chronbach's alpha was used to examine the reliability and principal component analysis was conducted to test the factor structure of the scale. The scale was found to have low internal consistency reliability (Chronbach's alpha = .58). Two factors were identified, accounting for 57% of the total variance. A series of chi-square analyses found that men indicated more symptoms associated with nicotine dependence than women (ps < .05). Although the poor reliability observed in the present sample argues for a cautious approach when assessing nicotine dependence among khat users, the findings on factor structure and gender differences may provide support for the validity of the scale. Taking into account sociocultural factors associated with patterns of smoking behavior among this population should improve the psychometric properties of FTND. PMID:23457896

  18. Adolescent Deviant Peer Clustering as an Amplifying Mechanism Underlying the Progression from Early Substance Use to Late Adolescent Dependence

    PubMed Central

    Van Ryzin, Mark J.; Dishion, Thomas J.

    2014-01-01

    Background Early substance use co-occurs with youths’ self-organization into deviant peer groups in which substance use is central to social interaction. We hypothesized that the social dynamics of deviant peer groups amplify the risk of progressing from early use to later dependence, and that this influence occurs over and above escalations in use that typically accompany early substance use and membership in deviant groups. Methods Our study used a longitudinal, multimethod dataset consisting of 998 adolescents and their families. Participants were recruited from middle schools in a large metropolitan area in the Pacific Northwest. The sample was 47.3% female and ethnically diverse (42.3% European-American, 29.1% African-American, and 28.6% other, including biracial). We examined deviant peer clustering as a mediator between early substance use and later dependence, controlling for proximal levels of use, SES, early antisocial behavior, and parental monitoring. Tobacco, alcohol, and marijuana use were assessed at ages 12, 13, and 16–17. Past-year nicotine, alcohol, and marijuana dependence (DSM-IV) was assessed at age 19. Youth and parent reports and observational data were used to assess deviant peer clustering at age 16–17, and youth reported on antisocial behavior and parental monitoring at ages 12 and 13. Results Early substance use predicted increased likelihood of dependence on tobacco, alcohol, and marijuana by late adolescence. Deviant peer affiliation mediated these links, even when accounting for proximal levels of substance use. Conclusions Early substance use not only promotes escalations in use across adolescence but also provides entry into a deviant social context that contributes to increased risk of dependence. Our results emphasize the importance of identifying and intervening in early substance use before it becomes an organizing factor in friendship selection and interaction. Deviant peer clusters are clearly an important avenue for

  19. 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

  20. 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

  1. Analysis of Detailed Phenotype Profiles Reveals CHRNA5-CHRNA3-CHRNB4 Gene Cluster Association With Several Nicotine Dependence Traits

    PubMed Central

    Broms, Ulla; Wedenoja, Juho; Largeau, Marine R.; Korhonen, Tellervo; Pitkäniemi, Janne; Keskitalo-Vuokko, Kaisu; Häppölä, Anja; Heikkilä, Katri H.; Heikkilä, Kauko; Ripatti, Samuli; Sarin, Antti-Pekka; Salminen, Outi; Paunio, Tiina; Pergadia, Michele L.; Madden, Pamela A. F.; Kaprio, Jaakko

    2012-01-01

    Introduction: The role of the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25 in the etiology of nicotine dependence (ND) is still being defined. In this study, we included all 15 tagging single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster and tested associations with 30 smoking-related phenotypes. Methods: The study sample was ascertained from the Finnish Twin Cohort study. Twin pairs born 1938–1957 and concordant for a history of cigarette smoking were recruited along with their family members (mainly siblings), as part of the Nicotine Addiction Genetics consortium. The study sample consisted of 1,428 individuals (59% males) from 735 families, with mean age 55.6 years. Results: We detected multiple novel associations for ND. DSM-IV ND symptoms associated significantly with the proxy SNP Locus 1 (rs2036527, p = .000009) and Locus 2 (rs578776, p = .0001) and tolerance factor of the Nicotine Dependence Syndrome Scale (NDSS) showed suggestive association to rs11636753 (p = .0059), rs11634351 (p = .0069), and rs1948 (p = .0071) in CHRNB4. Furthermore, we report significant association with DSM-IV ND diagnosis (rs2036527, p = .0003) for the first time in a Caucasian population. Several SNPs indicated suggestive association for traits related to ages at smoking initiation. Also, rs11636753 in CHRNB4 showed suggestive association with regular drinking (p = .0029) and the comorbidity of depression and ND (p = .0034). Conclusions: We demonstrate novel associations of DSM-IV ND symptoms and the NDSS tolerance subscale. Our results confirm and extend association findings for other ND measures. We show pleiotropic effects of this gene cluster on multiple measures of ND and also regular drinking and the comorbidity of ND and depression. PMID:22241830

  2. A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations

    PubMed Central

    Lind, Penelope A; Macgregor, Stuart; Vink, Jacqueline M; Pergadia, Michele L; Hansell, Narelle K; de Moor, Marleen HM; Smit, August B; Hottenga, Jouke-Jan; Richter, Melinda M; Heath, Andrew C; Martin, Nicholas G; Willemsen, Gonneke; de Geus, Eco JC; Vogelzangs, Nicole; Penninx, Brenda W; Whitfield, John B; Montgomery, Grant W; Boomsma, Dorret I; Madden, Pamela AF

    2011-01-01

    Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically-influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genome wide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (i) AD, 1224 cases and 1162 controls; (ii) ND, 1273 cases and 1113 controls; and (iii) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5×10−8) for ND (rs964170 in ARHGAP10 on chromosome 4, p=4.43×10−8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p=1.90×10−9), rs1784300 near DDX6 on chromosome 11 (p=2.60×10−9) and rs12882384 in KIAA1409 on chromosome 14 (p=4.86×10−8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be required before the detailed causes of comorbidity between AD and ND are understood. PMID:20158304

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls

    PubMed Central

    Janes, Amy C.; Nickerson, Lisa; Frederick, Blaise deB.; Kaufman, Marc J.

    2012-01-01

    Background Brain dysfunction in prefrontal cortex (PFC) and dorsal striatum (DS) contributes to habitual drug use. These regions are constituents of brain networks thought to be involved in drug addiction. To investigate whether networks containing these regions differ between nicotine dependent female smokers and age-matched female non-smokers, we employed functional MRI (fMRI) at rest. Methods Data were processed with independent component analysis (ICA) to identify resting state networks (RSNs). We identified a subcortical limbic network and three discrete PFC networks: a medial prefrontal cortex (mPFC) network and right and left lateralized fronto-parietal networks common to all subjects. We then compared these RSNs between smokers and non-smokers using a dual regression approach. Results Smokers had greater coupling versus non-smokers between left fronto-parietal and mPFC networks. Smokers with the greatest mPFC-left fronto-parietal coupling had the most DS smoking cue reactivity as measured during an fMRI smoking cue reactivity paradigm. This may be important because the DS plays a critical role in maintaining drug-cue associations. Furthermore, subcortical limbic network amplitude was greater in smokers. Conclusions Our results suggest that prefrontal brain networks are more strongly coupled in smokers, which could facilitate drug-cue responding. Our data also are the first to document greater reward-related network fMRI amplitude in smokers. Our findings suggest that resting state PFC network interactions and limbic network amplitude can differentiate nicotine-dependent smokers from controls, and may serve as biomarkers for nicotine dependence severity and treatment efficacy. PMID:22459914

  8. 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 Central

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

    2014-01-01

    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 regulated signaling 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 hours but not 2 hours post-training, delineating time points for STM (2 hours) and LTM (4 hours and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 hours but not 2 hours 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. PMID:24457151

  9. Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues.

    PubMed

    McClernon, Francis J; Kozink, Rachel V; Rose, Jed E

    2008-08-01

    Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerström test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables. PMID:17987060

  10. Role of Nicotine Dependence in the Association between the Dopamine Receptor Gene DRD3 and Major Depressive Disorder

    PubMed Central

    Korhonen, Tellervo; Loukola, Anu; Wedenoja, Juho; Nyman, Emma; Latvala, Antti; Broms, Ulla; Häppölä, Anja; Paunio, Tiina; Schrage, Andrew J.; Vink, Jaqueline M.; Mbarek, Hamdi; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Pergadia, Michele L.; Madden, Pamela A. F.; Kaprio, Jaakko

    2014-01-01

    Background The aims of this study were to analyze associations of dopamine receptor genes (DRD1-5) with Major Depressive Disorder (MDD) and nicotine dependence (ND), and to investigate whether ND moderates genetic influences on MDD. Methods The sample was ascertained from the Finnish Twin Cohort. Twin pairs concordant for smoking history were recruited along with their family members, as part of the multisite Nicotine Addiction Genetics consortium. Genetic association analyses were based on 1428 adults. Total of 70 tagging single nucleotide polymorphisms within the dopamine receptor genes were genotyped and analyzed for association with MDD, ND, and MD-ND co-morbidity. Individual level logistic regression analyses were based on 1296 adults with data on ND and MDD diagnoses, as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use. Four independent samples, such as population-based and case-control samples, were used for replication. Results Rs2399496, located 1.5 kb downstream of DRD3, showed suggestive association for MDD (p = 0.00076) and significant association for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND-interaction justified analyses by genetic risk variant and ND status. Individuals with ND and two minor alleles (AA) of rs2399496 had almost six-fold risk for MDD (OR 5.74, 95%CI 3.12–10.5, p = 9.010e-09) compared to individuals without ND and with two major alleles (TT). Conclusions Significant association between a variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our results further suggest that nicotine dependence may potentiate the influence of the DRD3 genetic variant on MDD. PMID:24927283

  11. 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

  12. 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

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

    PubMed

    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 therapies, we

  14. 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

  15. Vanilloid receptors mediate adrenergic nerve- and CGRP-containing nerve-dependent vasodilation induced by nicotine in rat mesenteric resistance arteries

    PubMed Central

    Eguchi, Shinji; Tezuka, Satoko; Hobara, Narumi; Akiyama, Shinji; Kurosaki, Yuji; Kawasaki, Hiromu

    2004-01-01

    Previous studies showed that nicotine induces adrenergic nerve-dependent vasodilation that is mediated by endogenous calcitonin gene-related peptide (CGRP) released from CGRP-containing (CGRPergic) nerves. The mechanisms underlying the nicotine-induced vasodilation were further studied. Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine, and the perfusion pressure was measured with a pressure transducer. Perfusion of nicotine (1–100 μM) for 1 min caused concentration-dependent vasodilation. Capsazepine (vanilloid receptor-1 antagonist; 1–10 μM) and ruthenium red (inhibitor of vanilloid response; 1–30 μM) concentration-dependently inhibited the nicotine-induced vasodilation without affecting the vasodilator response to exogenous CGRP. Nicotine-induced vasodilation was not inhibited by treatment with 3,4-dihydroxyphenylalanine (DOPA) receptor antagonist (L-DOPA cyclohexyl ester; 0.001–10 μM), dopamine D1 receptor-selective antagonist (SCH23390; 1–10 μM), dopamine D2 receptor antagonist (haloperidol; 0.1–0.5 μM), ATP P2x receptor-desensitizing agonist (α,β-methylene ATP; 1–10 μM), adenosine A2 receptor antagonist (8(p-sulfophenyl)theophylline; 10–50 μM) or neuropeptide Y (NPY)-Y1 receptor antagonist (BIBP3226; 0.1–0.5 μM). Immunohistochemical staining of the mesenteric artery showed dense innervation of CGRP- and vanilloid receptor-1-positive nerves, with both immunostainings appearing in the same neuron. The mesenteric artery was also densely innervated by NPY-positive nerves. Double immunostainings showed that both NPY and CGRP immunoreactivities appeared in the same neuron of the artery. These results suggest that nicotine acts on presynaptic nicotinic receptors to release adrenergic neurotransmitter(s) or related substance(s), which then stimulate vanilloid receptor-1 on CGRPergic nerves, resulting in CGRP release and vasodilation. PMID:15249421

  16. Cannabis Withdrawal Among Detained Adolescents: Exploring the Impact of Nicotine and Race

    PubMed Central

    Soenksen, Shayna; Stein, L.A.R.; Brown, Joanna D.; Stengel, JoAnn R.; Rossi, Joseph S.; Lebeau, Rebecca

    2015-01-01

    Rates of marijuana use among detained youths are exceptionally high. Research suggests a cannabis withdrawal syndrome is valid and clinically significant; however, these studies have mostly been conducted in highly controlled laboratory settings with treatment-seeking, White adults. The present study analyzed archival data to explore the magnitude of cannabis withdrawal symptoms within a diverse sample of detained adolescents while controlling for tobacco use and investigating the impact of race on symptom reports. Adolescents recruited from a juvenile correctional facility (N=93) completed a background questionnaire and the Marijuana Withdrawal Checklist. Analyses revealed a significant main effect for level of tobacco use on severity of irritability, and for level of marijuana use on severity of craving to smoke marijuana and strange/wild dreams. Furthermore, a significant main effect for race was found with Black adolescents reporting lower withdrawal discomfort scores and experiencing less severe depressed mood, difficulty sleeping, nervousness/anxiety, and strange/wild dreams. Although exploratory, these findings may have significant clinical implications for providers in juvenile detention facilities, allowing the execution of proper medical and/or behavioral interventions to assist adolescents presenting with problematic cannabis and/or tobacco withdrawal. PMID:25705103

  17. The Fagerström test for nicotine dependence: do revisions in the item scoring enhance the psychometric properties?

    PubMed

    Korte, Kristina J; Capron, Daniel W; Zvolensky, Michael; Schmidt, Norman B

    2013-03-01

    Despite widespread use, considerable literature has shown that the Fagerström Test for Nicotine Dependence (FTND; Heatherton, Kozlowski, Frecker, & Fagerström, 1991) has questionable psychometric properties, generally reflecting relatively poor properties of reliability and validity. One factor that may be affecting the psychometric qualities of the scale is the use of a dichotomous, forced-choice response format for certain items, in which respondents are asked to answer each question with a Yes or No response. This scoring approach is especially problematic when used to measure dimensional constructs, such as nicotine dependence, in which a dimensional construct is forced into a categorical construct. The purpose of the current study was to examine whether revising the response format utilized in the FTND would lead to an enhancement in the psychometric properties of this scale. This question was examined by removing the forced-choice response criteria on items 2, 5, and 6 of the FTND and revising the response options to reflect a 4-point Likert response set (0 = never, 1 = sometimes, 2 = most of the time, 3 = always). Participants consisted of 343 smokers from the community. Results revealed that the revised scoring approach resulted in a significant incremental improvement in scale reliability and enhanced convergent validity, showing a stronger association with smoking outcomes than the FTQ or FTND. Findings are discussed in terms of recommendations for scale revision and usage. PMID:23254226

  18. Association between KCNJ6 (GIRK2) gene polymorphism rs2835859 and post-operative analgesia, pain sensitivity, and nicotine dependence.

    PubMed

    Nishizawa, Daisuke; Fukuda, Ken-ichi; Kasai, Shinya; Ogai, Yasukazu; Hasegawa, Junko; Sato, Naomi; Yamada, Hidetaka; Tanioka, Fumihiko; Sugimura, Haruhiko; Hayashida, Masakazu; Ikeda, Kazutaka

    2014-01-01

    G-protein-activated inwardly rectifying potassium (GIRK) channels are expressed in many tissues and activated by several Gi/o protein-coupled receptors, such as opioid and dopamine receptors, and thus are known to be involved in the modulation of opioid-induced analgesia, pain, and reward. We focused on a GIRK-channel subunit that plays a pivotal role in the brain, GIRK2, and investigated the contribution of genetic variations of the GIRK2 (KCNJ6) gene to individual differences in the sensitivity to opioid analgesia. In our initial linkage disequilibrium analysis, a total of 27 single-nucleotide polymorphisms (SNPs) were selected within and around the regions of the KCNJ6 gene. Among them, the rs2835859 SNP, for which associations with analgesia and pain have not been previously reported, was selected in the exploratory study as a potent candidate SNP associated with opioid analgesic sensitivity. The results were corroborated in further confirmatory study. Interestingly, this SNP was also found to be associated with sensitivity to both cold and mechanical pain, susceptibility to nicotine dependence, and successful smoking cessation. The results indicate that this SNP could serve as a marker that predicts sensitivity to analgesic and pain and susceptibility to nicotine dependence. PMID:25346042

  19. Nicotine and tobacco

    MedlinePlus

    Withdrawal from nicotine; Smoking - nicotine addiction and withdrawal; Smokeless tobacco - nicotine addiction; Cigar smoking; Pipe smoking; Smokeless snuff; Tobacco use; Chewing tobacco; Nicotine addiction and tobacco

  20. Evidence for functional atypical nicotinic receptors that activate K+-dependent Cl- secretion in mouse tracheal epithelium.

    PubMed

    Hollenhorst, Monika I; Lips, Katrin S; Weitz, Ariane; Krasteva, Gabriela; Kummer, Wolfgang; Fronius, Martin

    2012-01-01

    The present study focused on the influence of nicotinic acetylcholine receptors (nAChR) on ion transport processes in mouse tracheal epithelium. RT-PCR experiments revealed expression of the α3, α4, α5, α7, α9, α10, β2, and β4 nAChR subunits in mouse tracheal epithelium. In Ussing chamber recordings of mouse tracheae, apically applied nicotine (100 μM) induced a dose-dependent increase of the transepithelial short-circuit current (EC(50): 14.6 μM). The nicotine-induced effect (I(NIC)) was attenuated by mecamylamine (25 μM, apical) and methyllycaconitine (1 μM, apical). The nAChR agonist 1.1-dimethyl-4-phenylpiperatinium iodide (DMPP) (100 μM) revealed apical and basolateral location of the receptors. I(NIC) was not affected by the sodium channel inhibitor amiloride (10 μM, apical) or the cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172 (20 μM, apical) but was reduced by the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 μM, apical), the Na(+)/K(+)/2Cl(-) cotransporter inhibitor bumetanide (200 μM, basolateral), the potassium channel inhibitor Ba(2+) (5 mM, basolateral), and 4.4'-diisothiocyanatostilbene-2.2'-disulfonate (100 μM, apical), indicating a contribution of Ca(2+)-activated chloride channels and potassium channels. Removal of extracellular Na(+) (apical) or Ca(2+) (apical) did not influence I(NIC) but reduced the DMPP effect. Experiments with the Ca(2+)-ionophore A23187, a mix of 3-isobutyl-1-methylxanthine and forskolin, or the inositol-1,4,5-triphospate (IP(3)) receptor inhibitor 2-aminoethyl-diphenyl-borinate (75 μM, apical) decreased I(NIC), indicating a nicotine-mediated increase of intracellular Ca(2+) and cAMP levels involving the IP(3) signaling pathway. These findings indicate the activity of Ca(2+)-permeable nAChRs and alternative metabotropic pathways by nAChR activation that mediate Cl(-) and K(+) transport in tracheal epithelium. PMID:21852683

  1. 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

  2. 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

  3. 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…

  4. Predictors of quitting behaviour with special reference to nicotine dependence among adult tobacco-users in a slum of Burdwan district, West Bengal, India

    PubMed Central

    Islam, Kamirul; Saha, Indranil; Saha, Rajib; Khan, Sufi Abdul Samim; Thakur, Rupali; Shivam, Swapnil

    2014-01-01

    Background & objectives: Information on predictors of quitting behaviour in adult tobacco users is scarce in Indian context. Hence, this study was undertaken to assess the intention of tobacco-users towards quitting and its predictors with reference to nicotine dependence. Methods: A community-based observational, cross-sectional study was conducted on 128 adult tobacco-users (89.8% male) with mean age of 41.1 ± 15.7 yr selected by complete enumeration method. Data were collected by interview using pre-designed, pre-tested schedule. Nicotine dependence was assessed by Fagerström Test for Nicotine Dependence (FTND) questionnaire. Result: Of the 128 users, 63.3 per cent had intention to quit. Majority of the tobacco users who did not intend to quit belonged to the age group of >40 yr (66.0%), were illiterate (55.3%), started tobacco use at 11 – 15 yr of age (57.4%), had been using tobacco for 20 yr or more (70.2%), were daily tobacco users (91.5%), and highly dependent on nicotine (80.9%). Tobacco users having high FTND score and who started tobacco use early in life were 1.83 and 3.30 times more unintended to quit, respectively. Interpretation & conclusions: Suitable plan for quitting should be developed depending on the FTND score of an individual, the most important determinant of quitting that would be beneficial for categorization of the treatment leading to successful quitting. PMID:24927353

  5. The Relationship of DSM-IV Personality Disorders to Nicotine Dependence-Results from a National Survey*

    PubMed Central

    Pulay, Attila J.; Stinson, Frederick S.; Ruan, W. June; Smith, Sharon M.; Pickering, Roger P.; Dawson, Deborah A; Grant, Bridget F.

    2010-01-01

    This study examined the prevalence of nicotine dependence (ND) and its associations with DSM-IV personality disorders (PDs) among current smokers (n=7,078), controlling for sociodemographic characteristics and comorbid Axis I and II disorders. Data were derived from a nationally representative sample of the U.S. population. Although all PDs were significantly associated with ND when sociodemographic factors were controlled, only schizotypal, borderline, narcissistic and obsessive-compulsive PDs were associated with ND after adding controls for Axis I and other Axis II disorders. These associations remained significant after controlling for degree of smoking exposure. The results suggest that both shared and PD-specific pathogenetic factors underlie these PD-ND associations. Implications are also discussed in terms of the relationship between personality features of schizotypal, borderline, narcissistic and obsessive-compulsive PDs and the self-medication hypothesis and the role of neurotransmission. PMID:20079976

  6. 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

  7. A twin association study of nicotine dependence with markers in the CHRNA3 and CHRNA5 genes.

    PubMed

    Maes, Hermine H; Neale, Michael C; Chen, Xiangning; Chen, Jingchun; Prescott, Carol A; Kendler, Kenneth S

    2011-09-01

    Twin and family studies have provided overwhelming evidence for the genetic basis of individual differences in tobacco initiation (TI), regular smoking (RS) and nicotine dependence (ND). However, only a few genes have been reliably associated with ND. We used a finite mixture distribution model to examine the significance and effect size of the association of previously identified and replicated specific variants in the CHRNA5 and CHRNA3 receptor genes with ND, against the background of genetic and environmental risk factors for ND. We hypothesize that additional phenotypic information in relatives who have not been genotyped can be used to increase the power of detecting the genetic variant. The nicotine measures were assessed by personal interview in female, male and opposite sex twin pairs (N = 4,153) from the population-based Virginia Twin Registry. Three SNPs in the CHRNA5 and CHRNA3 receptor genes, previously shown to be significantly associated with ND in this sample, were replicated in the augmented analyses; they accounted for less than one percent of the genetic variance in liability to ND, which is estimated to be over 50% of the phenotypic variance. The significance of these effects was increased by adding twins with phenotype but without genotype data, but gains are limited and variable. The SNPs associated with ND did not show a significant association with either TI or RS and appear to be specific to the addictive stage of ND, characterized by current smoking and smoking a large amount of cigarettes per day. Furthermore, these SNPs did not appear to be associated with the remaining items comprising the FTND scale. This study confirmed a significant contribution of the CHRNA receptor on different forms of tobacco dependence. However, the genetic variant only accounted for little of the total genetic variance for liability to ND. Including phenotypic data on ungenotyped relatives can improve the statistical power to detect the effects of genetic

  8. 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…

  9. The cholesterol dependence of activation and fast desensitization of the nicotinic acetylcholine receptor.

    PubMed Central

    Rankin, S E; Addona, G H; Kloczewiak, M A; Bugge, B; Miller, K W

    1997-01-01

    When nicotinic acetylcholine receptors are reconstituted into lipid bilayers lacking cholesterol, agonists no longer stimulate cation flux. The kinetics of this process are difficult to study because variations in vesicle morphology cause errors in flux measurements. We developed a new stopped-flow fluorescence assay to study activation independently of vesicle morphology. When receptors were rapidly mixed with agonist plus ethidium, the earliest fluorescence increase reported the fraction of channels that opened and their apparent rate of fast desensitization. These processes were absent when the receptor was reconstituted into dioleoylphosphatidylcholine or into a mixture of that lipid with dioleoylphosphatidic acid (12 mol%), even though a fluorescent agonist reported that resting-state receptors were still present. The agonist-induced channel opening probability increased with bilayer cholesterol, with a midpoint value of 9 +/- 1.7 mol% and a Hill coefficient of 1.9 +/- 0.69, reaching a plateau above 20-30 mol% cholesterol that was equal to the native value. On the other hand, the observed fast desensitization rate was comparable to that for native membranes from the lowest cholesterol concentration examined (5 mol%). Thus the ability to reach the open state after activation varies with the cholesterol concentration in the bilayer, whereas the rate of the open state to fast desensitized state transition is unaffected. The structural basis for this is unknown, but an interesting corollary is that the channels of newly synthesized receptors are not fully primed by cholesterol until they are inserted into the plasma membrane--a novel form of posttranslational processing. PMID:9370438

  10. 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

  11. 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

  12. 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…

  13. 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

  14. Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample

    PubMed Central

    Loukola, Anu; Wedenoja, Juho; Keskitalo-Vuokko, Kaisu; Broms, Ulla; Korhonen, Tellervo; Ripatti, Samuli; Sarin, Antti-Pekka; Pitkäniemi, Janne; He, Liang; Häppölä, Anja; Heikkilä, Kauko; Chou, Yi-Ling; Pergadia, Michele L; Heath, Andrew C; Montgomery, Grant W; Martin, Nicholas G; Madden, Pamela AF; Kaprio, Jaakko

    2013-01-01

    Smoking is a major risk factor for several somatic diseases, and is also emerging as a causal factor for neuropsychiatric disorders. Genome-wide association (GWA) and candidate gene studies for smoking behavior and nicotine dependence (ND) have disclosed too few predisposing variants to account for the high estimated heritability. Prior large-scale GWA studies have had very limited phenotypic definitions of relevance to smoking-related behavior, which has likely impeded the discovery of genetic effects. We performed genome-wide association analyses on 1114 adult twins ascertained for ever smoking from the population-based Finnish Twin Cohort study. The availability of 17 smoking-related phenotypes allowed us to comprehensively portray the dimensions of smoking behavior, clustered into the domains of smoking initiation, amount smoked, and ND. Our results highlight a locus on 16p12.3, with several SNPs in the vicinity of CLEC19A showing association (P<1×10−6) with smoking quantity. Interestingly, CLEC19A is located close to a previously reported attention deficit hyperactivity disorder (ADHD) linkage locus and an evident link between ADHD and smoking has been established. Intriguing preliminary association (P<1×10−5) was detected between DSM-IV ND diagnosis and several SNPs in ERBB4, coding for a Neuregulin receptor, on 2q33. The association between ERBB4 and DSM-IV ND diagnosis was replicated in an independent Australian sample. Interestingly, in the paper by Turner et al., significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice. Turner et al. also detected an association between NRG3 SNPs and smoking cessation success in a clinical trial. ERBB4 has previously been associated with schizophrenia; further, it is located within an established schizophrenia linkage locus and within a linkage locus for a smoker phenotype identified in this sample. As a conclusion, we disclose novel

  15. 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

  16. 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. PMID:26475784

  17. Real-time fMRI in the Treatment of Nicotine Dependence: A Conceptual Review and Pilot Studies

    PubMed Central

    Hartwell, Karen J.; Prisciandaro, James J.; Borckardt, Jeffery; Li, Xingbao; George, Mark S.; Brady, Kathleen T.

    2012-01-01

    Technical advances allowing for the analysis of fMRI results in real-time have led to studies exploring the ability of individuals to use neural feedback signals to modify behavior and regional brain activation. The use of real-time fMRI (rtfMRI) feedback has been explored for therapeutic benefit in a number of disease states, but to our knowledge the potential therapeutic benefit of rtfMRI feedback in the treatment of addictive disorders has not been explored. This manuscript will provide an overview of the development of rtfMRI and discussion of its potential uses in the treatment of addictions. We also describe a series of pilot studies that highlight some of the technical challenges in developing a rtfMRI feedback paradigm for use in addictions, specifically in nicotine dependence. Because the use of rtfMRI feedback is in its infancy, the work described is focused on establishing some of the basic parameters in optimizing the rtfMRI feedback, such as the type of feedback signal, region of interest for feedback and predicting which subjects are most likely to respond well to training. While rtfMRI feedback remains an intriguing possibility for the treatment of addictions, much work remains to be done in establishing its efficacy. PMID:22564200

  18. Inhalant Abuse and Dependence among Adolescents in the United States

    ERIC Educational Resources Information Center

    Wu, Li-Tzy; Pilowsky, Daniel J.; Schlenger, William E.

    2004-01-01

    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…

  19. 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

  20. Nicotine Gum

    MedlinePlus

    ... gum is used to help people stop smoking cigarettes. Nicotine chewing gum should be used together with ... by your doctor.If you smoke your first cigarette more than 30 minutes after waking up, use ...

  1. 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

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

    PubMed

    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 (6mg/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 GABA(A) 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 Mg(2+) 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

  3. 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.

  4. 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

  5. Nicotinic acetylcholine receptors induce c-Kit ligand/Stem Cell Factor and promote stemness in an ARRB1/ β-arrestin-1 dependent manner in NSCLC

    PubMed Central

    Perumal, Deepak; Pillai, Smitha; Nguyen, Jonathan; Schaal, Courtney; Coppola, Domenico; Chellappan, Srikumar P.

    2014-01-01

    Lung cancer remains the leading cause of cancer-related deaths worldwide. β-arrestin-1 (ARRB1), a scaffolding protein involved in the desensitization of signals arising from activated G-protein-coupled receptors (GPCRs), has been shown to play a role in invasion and proliferation of cancer cells, including nicotine-induced proliferation of human non–small cell lung cancers (NSCLCs). In this study, we identified genes that are differentially regulated by nicotine in an ARRB1/β-arrestin-1 dependent manner in NSCLC cells by microarray analysis. Among the identified genes, SCF (Stem cell factor) strongly differentiated smokers from non-smokers in the Director's Challenge Set expression data and its high expression correlated with poor prognosis. SCF, a major cytokine is the ligand for the c-Kit proto-oncogene and was found to be over expressed in human lung adenocarcinomas, but not squamous cell carcinomas. Data presented here show that transcription factor E2F1 can induce SCF expression at the transcriptional level and depletion of E2F1 or ARRB1/β-arrestin-1 could not promote self-renewal of SP cells. These studies suggest that nicotine might be promoting NSCLC growth and metastasis by inducing the secretion of SCF, and raise the possibility that targeting signalling cascades that activate E2F1 might be an effective way to combat NSCLC. PMID:25401222

  6. Nicotine Related Brain Activity: The Influence Of Smoking History and Blood Nicotine Levels, an Exploratory Study

    PubMed Central

    Yamamoto, Rinah T.; Rohan, Michael L.; Goletiani, Nathalie; Olson, David; Peltier, MacKenzie; Renshaw, Perry F.; Mello, Nancy K.

    2012-01-01

    OBJECTIVE In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI). METHODS phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects’ nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of Smoking history and physiological measures on the response to nicotine were also investigated. RESULTS Greater lifetime exposure to cigarette smoking was significantly correlated with higher peak serum nicotine levels. PhMRI analysis of the differential response of nicotine compared to the saline condition showed distinctive activation patterns when analyzed with a) the nicotine time course, b) nicotine time course controlling for smoking history (pack years), and c) pack years controlling for nicotine. CONCLUSIONS These results suggest that smoking exposure history influences serum nicotine levels and the brain’s response to nicotine. Alterations in brain activity may be a result of vascular and neuro-adaptations involved in drug exposure and addiction. PMID:23117126

  7. Determining the Causes and Consequences of Nicotine Dependence: Emerging Genetic Research Methods

    PubMed Central

    Ware, Jennifer J.; Munafò, Marcus R.

    2016-01-01

    Tobacco use remains the leading cause of preventable death worldwide. Establishing the genetic aetiology of tobacco use and dependence is an important first step in understanding the neurobiological mechanisms of tobacco use, and in turn the development of effective treatments. In addition, whilst the effects of tobacco use on a broad range of physical illnesses (e.g., lung cancer, respiratory disease, cardiovascular disease) are now well-established, the causal effects of tobacco use on a number of other outcomes remains to be established. Determining the causes and consequences of tobacco use therefore continues to be both a scientific and a public health priority. Here we review emerging methods in genetic research that allow stronger causal inferences to be drawn from observational data. PMID:25135777

  8. Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen.

    PubMed

    Silva, Rangel L; Castanheira, Fernanda V; Figueiredo, Jozi G; Bassi, Gabriel S; Ferreira, Sérgio H; Cunha, Fernando Q; Cunha, Thiago M; Kanashiro, Alexandre

    2016-08-01

    The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta-adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor. PMID:27262431

  9. 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…

  10. Nicotine: abused substance and therapeutic agent.

    PubMed Central

    Le Houezec, J

    1998-01-01

    Tobacco dependence is a complex phenomenon that is not fully understood. Nicotine is the main alkaloid in tobacco and the addictive compound of tobacco. It can improve both mood and cognitive functioning; these positive effects are strong reinforcements for smokers and contribute to their addiction. Opposite results also have been reported, however, and the effects of nicotine remain controversial. Recent epidemiological and empirical studies have indicated that smoking or nicotine or both may have protective effects against certain diseases. These findings have suggested that nicotine may be used as a therapeutic agent. However, because a variety of nicotinic cholinergic receptors are present in the brain, new agonist compounds may prove to be more effective than nicotine for therapeutic purposes. Studies are reviewed and the suggestion made that nicotine may prove useful as a tool to help us understand normal and pathological brain functioning. PMID:9549250

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Nicotine Lozenges

    MedlinePlus

    ... is stopped and to reduce the urge to smoke. ... often than prescribed by your doctor.If you smoke your first cigarette within 30 minutes of waking ... should use 4-mg nicotine lozenges. If you smoke your first cigarette more than 30 minutes after ...

  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. 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

  19. Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats.

    PubMed

    Lee, Jun-Yeob; Choi, Mee Jung; Choe, Eun Sang; Lee, Young-Ju; Seo, Joung-Wook; Yoon, Seong Shoon

    2016-06-01

    Although it is widely accepted that nicotine plays a key role in tobacco dependence, nicotine alone cannot account for all of the pharmacological effects associated with cigarette smoke found in preclinical models. Thus, the present study aimed to determine the differential effects of the interoceptive cues of nicotine alone versus those of cigarette smoke condensate (CSC) in nicotine-trained rats. First, the rats were trained to discriminate nicotine (0.4mg/kg, subcutaneous [s.c.]) from saline in a two-lever drug discrimination paradigm. Then, to clarify the different neuropharmacological mechanisms underlying the discriminative-stimulus effects in the nicotine and CSC in nicotine-trained rats, either the α4β2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (DHβE; 0.3-1.0mg/kg, s.c.) or the α7 nAChR antagonist methyllycaconitine citrate (MLA; 5-10mg/kg, intraperitoneal [i.p.]) was administered prior to the injection of either nicotine or CSC. Separate set of experiments was performed to compare the duration of action of the discriminative-stimulus effects of CSC and nicotine. CSC exhibited a dose-dependent nicotine generalization, and interestingly, 1.0mg/kg of DHβE antagonized the discriminative effects of nicotine (0.4mg/kg) but not CSC (0.4mg/kg nicotine content). However, pretreatment with MLA had no effect. In the time-course study, CSC had a relatively longer half-life in terms of the discriminative-stimulus effects compared with nicotine alone. Taken together, the present findings indicate that CSC has a distinct influence on interoceptive effects relative to nicotine alone and that these differential effects might be mediated, at least in part, by the α4β2, but not the α7, nAChR. PMID:26996314

  20. The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat

    PubMed Central

    Paterson, Neil E.; Semenova, Svetlana; Markou, Athina

    2008-01-01

    Rationale Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence. Objectives To evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats. Methods A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic minipumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via minipump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing minipumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure. Results Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding. Conclusions The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal, and may alter the rewarding effects of nicotine and food. PMID:18438738

  1. Nicotine Transdermal Patch

    MedlinePlus

    ... patches are used to help people stop smoking cigarettes. They provide a source of nicotine that reduces ... cause harm to the fetus.do not smoke cigarettes or use other nicotine products while using nicotine ...

  2. Effect of nicotine on negative affect among more impulsive smokers.

    PubMed

    Doran, Neal; McChargue, Dennis; Spring, Bonnie; VanderVeen, Joe; Cook, Jessica Werth; Richmond, Malia

    2006-08-01

    In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation. PMID:16893271

  3. 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

  4. Common genetic risk of major depression and nicotine dependence: the contribution of antisocial traits in a United States veteran male twin cohort.

    PubMed

    Fu, Qiang; Heath, Andrew C; Bucholz, Kathleen K; Lyons, Michael J; Tsuang, Ming T; True, William R; Eisen, Seth A

    2007-06-01

    Many studies that found associations between depression and nicotine dependence have ignored possible shared genetic influences associated with antisocial traits. The present study examined the contribution of genetic and environmental effects associated with conduct disorder (CD) and antisocial personality disorder (ASPD) to the comorbidity of major depression (MD) and nicotine dependence (ND). A telephone diagnostic interview, the Diagnostic Interview Schedule-III-R, was administered to eligible twins from the Vietnam Era Twin (VET) Registry in 1992. Multivariate genetic models were fitted to 3360 middle-aged and predominantly white twin pairs (1868 monozygotic, 1492 dizygotic pairs) of which both members completed the pertinent diagnostic interview sections. Genetic influences on CD accounted for 100%, 68%, and 50% of the total genetic variance in risk for ASPD, MD and ND, respectively. After controlling for genetic influences on CD, the partial genetic correlation between MD and ND was no longer statistically significant. Nonshared environmental contributions to the comorbidity among these disorders were not significant. This study not only demonstrates that the comorbidity between ND and MD is influenced by common genetic risk factors, but also further suggests that the common genetic risk factors overlapped with those for antisocial traits such as CD and ASPD in men. PMID:17564505

  5. Accelerated desensitization of nicotinic receptor channels and its dependence on extracellular calcium in isolated skeletal muscles of streptozotocin-diabetic mice.

    PubMed Central

    Nojima, H.; Tsuneki, H.; Kimura, I.; Kimura, M.

    1995-01-01

    1. To elucidate the influence of the diabetic state on desensitization of nicotinic acetylcholine (ACh) receptor channels, we investigated the time course of the decrease in amplitude of ACh potentials elicited by iontophoretic application to isolated diaphragm muscle of streptozotocin-diabetic mice. We also investigated time- and extracellular Ca(2+)-dependent changes in the channel opening frequency of ACh-activated channel currents and the involvement of protein kinases by use of the cell-attached patch clamp technique in single skeletal muscle cells. 2. When ACh potentials were evoked at 10 Hz, the decline in trains of ACh potentials was accelerated in the diabetic state. 3. The time-dependent decrease in the channel opening frequency of diabetic muscle cells was greatly accelerated compared with normal cells in 2.5 mM Ca2+ medium. 4. This accelerated decrease in channel opening frequency was restored by pretreatment with a protein kinase C inhibitor, staurosporine (10 nM) but neither a protein kinase A inhibitor, H-89 (3 microM) nor a calmodulin kinase II inhibitor, KN-62 (5 microM) were able to restore the fall in opening frequency. 5. These results demonstrate that in the diabetic state the desensitization of nicotinic ACh receptor channels may be greatly accelerated by activating protein kinase C, which is caused by an increase in the amount of available intracellular Ca2+. PMID:8564237

  6. Pharmacogenetics of nicotine and associated smoking behaviors.

    PubMed

    Tanner, Julie-Anne; Chenoweth, Meghan J; Tyndale, Rachel F

    2015-01-01

    This chapter summarizes genetic factors that contribute to variation in nicotine pharmacokinetics and nicotine's pharmacological action in the central nervous system (CNS), and how this in turn influences smoking behaviors. Nicotine, the major psychoactive compound in cigarette smoke, is metabolized by a number of enzymes, including CYP2A6, CYP2B6, FMOs, and UGTs, among others. Variation in the genes encoding these enzymes, in particular CYP2A6, can alter the rate of nicotine metabolism and smoking behaviors. Faster nicotine metabolism is associated with higher cigarette consumption and nicotine dependence, as well as lower quit rates. Variation in nicotine's CNS targets and downstream signaling pathways can also contribute to interindividual differences in smoking patterns. Binding of nicotine to neuronal nicotinic acetylcholine receptors (nAChRs) mediates the release of several neurotransmitters including dopamine and serotonin. Genetic variation in nAChRs, and in transporter and enzyme systems that leads to altered CNS levels of dopamine and serotonin, is associated with a number of smoking behaviors. To date, the precise mechanism underpinning many of these findings remains unknown. Considering the complex etiology of nicotine addiction, a more comprehensive approach that assesses the contribution of multiple gene variants, and their interaction with environmental factors, will likely improve personalized therapeutic approaches and increase smoking cessation rates. PMID:25655887

  7. Urban Adolescents' Perceptions of Their Neighborhoods: An Examination of Spatial Dependence

    ERIC Educational Resources Information Center

    Bass, Judith K.; Lambert, Sharon F.

    2004-01-01

    Spatial dependence exists when the variation between observations is dependent on spatial location. In the present study, geostatistical methods were used to examine spatial dependence in adolescents' perceptions of their neighborhoods: whether adolescents living in close proximity perceived their neighborhoods more similarly than adolescents…

  8. 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

  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. 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

  11. Response disinhibition evoked by the administration of nicotine and nicotine-associated contextual cues

    PubMed Central

    Kirshenbaum, Ari P.; Johnson, Matthew W.; Schwarz, Sarah L.; Jackson, Eric R.

    2009-01-01

    Nicotine causes dose-dependent alterations in accuracy on the differential-reinforcement of low-rate responding (DRL) 29.5-s schedule in rats. The current investigation evaluated whether nicotine-associated contextual cues can produce nicotine-like perturbations in DRL-schedule performance in the absence of nicotine. Nicotine and saline administrations occurred just prior to DRL 29.5-s schedule responding for sucrose solution, and two different experimental contexts (differentiated by visual, olfactory, and tactile cues) were utilized. All subjects (N = 16) experienced two consecutive daily sessions of DRL-schedule responding per day. The experimental group (n = 8) was exposed to saline immediately prior to the first session and 0.3mg/kg nicotine before the second session, and the context was changed between sessions. This sequence of saline and then nicotine administration, paired with two reliable contexts, persisted for 12 consecutive days and successive nicotine administrations corresponded with increasingly poorer performance on the DRL 29.5-s schedule. No nicotine was administered for days 13–20 during context testing, and the nicotine-associated context produced response disinhibition on the DRL schedule. Two control groups were included in the design; subjects in one control group (n = 4) received saline in each context to verify that the contexts themselves were not exerting control over operant responding. To assess how explicit and non-explicit pairings of nicotine and contextual cues influenced DRL behavior, subjects in a second control group (n = 4) were given nicotine prior to the second session, but the contexts were not altered between sessions. The results from this experiment suggest that environmental stimuli associated with nicotine exposure can come to elicit nicotine-induced performance decrements on a DRL 29.5-s schedule. PMID:19640659

  12. Protecting Children From Tobacco, Nicotine, and Tobacco Smoke.

    PubMed

    Farber, Harold J; Groner, Judith; Walley, Susan; Nelson, Kevin

    2015-11-01

    This technical report serves to provide the evidence base for the American Academy of Pediatrics' policy statements "Clinical Practice Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke" and "Public Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke." Tobacco use and involuntary exposure are major preventable causes of morbidity and premature mortality in adults and children. Tobacco dependence almost always starts in childhood or adolescence. Electronic nicotine delivery systems are rapidly gaining popularity among youth, and their significant harms are being documented. In utero tobacco smoke exposure, in addition to increasing the risk of preterm birth, low birth weight, stillbirth, placental abruption, and sudden infant death, has been found to increase the risk of obesity and neurodevelopmental disorders. Actions by pediatricians can help to reduce children's risk of developing tobacco dependence and reduce children's involuntary tobacco smoke exposure. Public policy actions to protect children from tobacco are essential to reduce the toll that the tobacco epidemic takes on our children. PMID:26504135

  13. 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

  14. 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

  15. 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

  16. 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…

  17. Nicotinic Receptor Antagonists as Treatments for Nicotine Abuse

    PubMed Central

    Crooks, Peter A.; Bardo, Michael T.; Dwoskin, Linda P.

    2014-01-01

    Despite the proven efficacy of current pharmacotherapies for tobacco dependence, relapse rates continue to be high, indicating that novel medications are needed. Currently, several smoking cessation agents are available, including varenicline (Chantix®), bupropion (Zyban®), and cytisine (Tabex®). Varenicline and cytisine are partial agonists at the α4β2* nicotinic acetylcholine receptor (nAChR). Bupropion is an antidepressant but is also an antagonist at α3β2* ganglionic nAChRs. The rewarding effects of nicotine are mediated, in part, by nicotine-evoked dopamine (DA) release leading to sensitization, which is associated with repeated nicotine administration and nicotine addiction. Receptor antagonists that selectivity target central nAChR subtypes mediating nicotine-evoked DA release should have efficacy as tobacco use cessation agents with the therapeutic advantage of a limited side-effect profile. While α-conotoxin MII (α-CtxMII)-insensitive nAChRs (e.g., α4β2*) contribute to nicotine-evoked DA release, these nAChRs are widely distributed in the brain, and inhibition of these receptors may lead to nonselective and untoward effects. In contrast, α-CtxMII-sensitive nAChRs mediating nicotine-evoked DA release offer an advantage as targets for smoking cessation, due to their more restricted localization primarily to dopaminergic neurons. Small drug-like molecules that are selective antagonists at α-CtxMII-sensitive nAChR subtypes that contain α6 and β2 subunits have now been identified. Early research identified a variety of quaternary ammonium analogs that were potent and selective antagonists at nAChRs mediating nicotine-evoked DA release. More recent data have shown that novel, non-quaternary bis-1,2,5,6-tetrahydropyridine analogs potently inhibit (IC50<1 nM) nicotine-evoked DA release in vitro by acting as antagonists at α-CtxMII-sensitive nAChR subtypes; these compounds also decrease NIC self-administration in rats. PMID:24484986

  18. 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.

  19. Animal Models of Nicotine Exposure: Relevance to Second-Hand Smoking, Electronic Cigarette Use, and Compulsive Smoking

    PubMed Central

    Cohen, Ami; George, Olivier

    2013-01-01

    Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use, and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake. PMID:23761766

  20. A functional polymorphism in the interleukin-1beta and severity of nicotine dependence in male schizophrenia: a case-control study.

    PubMed

    Zhang, Xiang Yang; Chen, Da-Chun; Tan, Yun-Long; Tan, Shu-ping; Luo, Xingguang; Zuo, Lingjun; Rao, Wenwang; Yu, Qiong; Kou, Changgui; Allen, Melissa; Correll, Christoph U; Wu, Jingqin; Soares, Jair C

    2015-05-01

    Previous studies have shown that the functional 511C/T polymorphism in the IL-1beta-gene may be implicated in the susceptibility for schizophrenia. Moreover, recent studies suggested that IL-1 participates in the progression of lung disease in smokers, which are overrepresented in schizophrenia. We aimed to investigate the possible relationship between the IL-1beta-511C/T polymorphism and smoking behavior in schizophrenia versus healthy controls in a Chinese population. The IL-1beta-511C/T polymorphism was genotyped in 638 male patients with chronic schizophrenia (smoker/never-smoker = 486/152) and 469 male controls (smoker/never-smoker = 243/226). The cigarettes smoked per day, the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for nicotine dependence (FTND) were assessed. Patients were also rated on the Positive and Negative Syndrome Scale (PANSS). The results showed no significant differences in genotype and allele distribution between patients and controls, and between smokers and never-smokers in either the patient or control group. However, in patients, smokers with the C/C genotype had significantly higher HSI (p < 0.005) and FTND (p < 0.05) scores than smokers with the T/T genotype, without significant differences in controls. Furthermore, there was a linear positive correlation between the number of C alleles and the HSI (p < 0.005) in patients. Our findings suggest that the IL-1beta-511C/T polymorphism may not be related to schizophrenia or smoking status in Chinese individuals, but may affect the severity of nicotine dependence among male smokers with schizophrenia. PMID:25858413

  1. 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.

  2. A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration.

    PubMed

    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

  3. 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

  4. Effect of Intraoperative and Postoperative Infusion of Dexmedetomidine on the Quality of Postoperative Analgesia in Highly Nicotine-Dependent Patients After Thoracic Surgery

    PubMed Central

    Ren, Chunguang; Zhang, Xuejun; Liu, Zhong; Li, Changying; Zhang, Zongwang; Qi, Feng

    2015-01-01

    Abstract Smoking is one of the most common addictions in the world. Nicotine inhalation could increase the risk of cardiorespiratory diseases. However, the solution that improved postoperative analgesia for highly nicotine-dependent patients undergoing thoracic surgery has not been specifically addressed. This CONSORT-prospective, randomized, double-blinded, controlled trial investigated the efficacy of combination of dexmedetomidine and sufentanil for highly nicotine (Fagerstrom test of nicotine dependence ≥6)-dependent patients after thoracic surgery. One hundred seventy-four male patients who underwent thoracic surgery were screened between February 2014 and November 2014, and a total of forty-nine were excluded. One hundred thirty-two highly nicotine-dependent male patients who underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia were divided into 3 groups after surgery in this double-blind, randomized study: sufentanil (0.02 μg/kg/h, Group S), sufentanil plus dexmedetomidine (0.02 μg/kg/h each, Group D1), or sufentanil (0.02 μg/kg/h) plus dexmedetomidine (0.04 μg/kg/h) (Group D2). The patient-controlled analgesia (PCA) program was programmed to deliver a bolus dose of 2 ml, with background infusion of 2 ml/h and a lockout of 5 min, 4-hour limit of 40 ml, as our retrospective study. The primary outcome measure was the cumulative amount of self-administered sufentanil; the secondary outcome measures were pain intensity (numerical rating scale, NRS), level of sedation (LOS), Bruggrmann comfort scale (BCS), functional activity score (FAS), and concerning adverse effects. The amount of self-administered sufentanil were lower in group D2 compared with S and D1 groups during the 72 hours after surgery (P < 0.05), whereas the total dosage and dosage per body weight of sufentanil were significantly lower in D1 group than that of S group only at 4, 8, and 16 hours after surgery (P < 0.05). Compared

  5. 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

  6. 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

  7. Association and interaction analysis of variants in CHRNA5/CHRNA3/CHRNB4 gene cluster with nicotine dependence in African and European Americans

    PubMed Central

    Li, Ming D.; Xu, Qing; Lou, Xiang-Yang; Payne, Thomas J; Niu, Tianhua; Ma, Jennie Z.

    2010-01-01

    Several previous genome-wide and targeted association studies revealed that variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster on chromosome 15 that encode the α5, α3 and β4 subunits of the nicotinic acetylcholine receptor (nAChRs) are associated with nicotine dependence (ND) in European Americans (EAs) or others of European origin. Considering the distinct linkage disequilibrium patterns in European and other ethnic populations such as African Americans (AAs), it would be interesting to determine whether such associations exist in other ethnic populations. We performed a comprehensive association and interaction analysis of the CHRNA5/A3/B4 cluster in two ethnic samples to investigate the role of variants in the risk for ND, which was assessed by Smoking Quantity, Heaviness Smoking Index, and Fagerström test for ND. Using a family-based association test, we found a nominal association of single nucleotide polymorphisms (SNPs) rs1317286 and rs8040868 in CHRNA3 with ND in the AA and combined AA and EA samples. Furthermore, we found that several haplotypes in CHRNA5 and CHRNA3 are nominally associated with ND in AA, EA, and pooled samples. However, none of these associations remained significant after correction for multiple testing. In addition, we performed interaction analysis of SNPs within the CHRNA5/A3/B4 cluster using the pedigree-based generalized multifactor dimensionality reduction method and found significant interactions within CHRNA3 and among the three subunit genes in the AA and pooled samples. Together, these results indicate that variants within CHRNA3 and among CHRNA5, CHRNA3, and CHRNB4 contribute significantly to the etiology of ND through gene-gene interactions, although the association of each subunit gene with ND is weak in both the AA and EA samples. PMID:19859904

  8. Acetylcholine-induced potassium current of guinea pig outer hair cells: its dependence on a calcium influx through nicotinic-like receptors.

    PubMed

    Blanchet, C; Eróstegui, C; Sugasawa, M; Dulon, D

    1996-04-15

    The cholinergic efferent inhibition of mammalian outer hair cells (OHCs) is mediated by a hyperpolarizing K+ current. We have made whole-cell tight-seal recordings from single OHCs isolated from the guinea pig cochlea to characterize the mechanism by which acetylcholine (ACh) activates K+ channels. After ACh application, OHCs exhibited a biphasic response: an early depolarizing current preceding the predominant hyperpolarizing K+ current. The current-voltage (I-V) relationship of the ACh-induced response displayed an N-shape, suggesting the involvement of Ca2+ influx. When whole-cell recording was combined with confocal calcium imaging, we simultaneously observed the ACh-induced K+ current (IK(ACh)) and a Ca2+ response restricted to the synaptic area of the cell. This IK(ACh) could be prevented by loading OHCs with 10 mM of the fast Ca2+ buffer bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (or BAPTA), therefore allowing the observation of the ACh-induced early current in isolation. This early current revealed nicotinic features because it activated with an intrinsic delay in the millisecond range, reversed nearly in between potassium and sodium equilibrium potentials, and was blocked by curare. However, it was strongly reduced in the absence of external Ca2+, and its I-V relationship displayed an unusual outward rectification at positive membrane potentials and an inward rectification below -60 mV. The results indicate that the cholinergic response of mammalian OHCs involves a "nicotinic-like" nonspecific cation channel through which Ca2+ enters and triggers activation of nearby Ca2+-dependent K+ channels. PMID:8786433

  9. Psychopharmacological interactions between nicotine and ethanol.

    PubMed

    Rose, Jed E; Brauer, Lisa H; Behm, Frederique M; Cramblett, Matthew; Calkins, Kevin; Lawhon, Dawn

    2004-02-01

    Epidemiological, clinical, and laboratory evidence has shown a positive correlation between cigarette smoking and ethanol use, and previous studies suggest some commonality in the neural pathways mediating effects of nicotine and ethanol. In this study, the subjective and behavioral interactions among nicotine, ethanol, and the nicotinic antagonist mecamylamine were investigated. The main objectives were to determine how the rewarding effects of nicotine might be modified by ethanol, and to compare the effects of ethanol with those of a nicotinic antagonist (mecamylamine). A total of 48 smokers who regularly consumed alcoholic beverages participated in four laboratory sessions presenting a 2 (nicotine vs. denicotinized cigarette smoke)x2 (10 mg oral mecamylamine hydrochloride vs. placebo)x2 (ethanol.5 g/kg vs. placebo) design, with ethanol as a between-subjects factor. Dependent measures included blood alcohol concentration (BAC), as assessed by breath alcohol detector; subjective drug effects; and rate of ad lib smoking during a 2-hr period. Results showed that peak BAC averaged.03 g/dl in the ethanol condition. Ethanol potentiated some of the subjective rewarding effects of nicotine, including smoking satisfaction, stimulant as well as calming effects, and relief of craving for cigarettes. During the ad lib smoking period, mecamylamine decreased satisfaction associated with the nicotine-containing cigarettes; mecamylamine also induced smoking but only in the placebo ethanol condition. These results highlight the potent interaction between ethanol and nicotinic systems, and suggest that ethanol can potentiate the rewarding effects of nicotine as well as offset some of the effects of a nicotinic antagonist. PMID:14982697

  10. Smoking Antecedents: Separating Between- and Within-Person Effects of Tobacco Dependence in a Multiwave Ecological Momentary Assessment Investigation of Adolescent Smoking

    PubMed Central

    2014-01-01

    Introduction: Ecological momentary assessment (EMA) investigations have shown that the antecedents of smoking vary with individual differences in tobacco dependence. This has been interpreted as indicating that the transition to dependence is characterized by an erosion of external stimulus control over smoking. Rigorously testing this requires collecting multiple waves of EMA data, which permits separation of the influence of between- and within-person tobacco dependence variation in multilevel models. Methods: Adolescents (n = 313, 9th or 10th grade at baseline) participated in up to 4 waves of week-long EMA assessment over the course of 2 years as part of a larger longitudinal, observational study. At each wave, participants recorded contextual features and subjective states in response to prompted diary assessments and when smoking. They completed a youth-specific form of the Nicotine Dependence Syndrome Scale at each wave. Results: In cross-sectional multilevel analyses, smoking was less contingent on alcohol/drug use and was more common at home and in the morning for adolescents with higher levels of dependence. Multiwave analyses demonstrated that these effects were largely attributable to between-person variation in dependence, although parameter estimates for intraindividual dependence × antecedent effects tended to be in the predicted direction. Discussion: Findings provided partial support for the contention that the antecedents of smoking shift as an individual progresses to higher levels of dependence. Distinctive choices concerning smoking settings also appear to reflect between-person differences in propensity to dependence. More generally, the findings illustrate the value of using multilevel modeling and repeated EMA assessments to investigate the correlates of tobacco dependence at different levels of analysis. PMID:23990475

  11. 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

  12. 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

  13. 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. PMID:26391161

  14. 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

  15. 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

  16. Nicotine replacement therapy

    MedlinePlus

    ... If wearing the patch at night causes odd dreams, try sleeping without the patch. People who smoke ... cessation - nicotine replacement; Tobacco - nicotine replacement therapy References American Cancer Society. Guide to quitting smoking. Last revised ...

  17. 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…

  18. 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

  19. 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

  20. R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

    PubMed Central

    Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Okunola-Bakare, Oluyomi M; Slack, Rachel D; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

    2015-01-01

    (±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans. PMID:25613829

  1. 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

  2. Tobacco/Nicotine and Endogenous Brain Opioids

    PubMed Central

    Xue, Yue; Domino, Edward F.

    2008-01-01

    Smoking is a major public health problem with devastating health consequences. Although many cigarette smokers are able to quit, equal numbers of others cannot! Standard medications to assist in smoking cessation, such as nicotine replacement therapies and bupropion, are ineffective in many remaining smokers. Recent developments in the neurobiology of nicotine dependence have identified several neurotransmitter systems that may contribute to the process of smoking maintenance and relapse. These include: especially dopamine, but also norepinephrine, 5-hydroxytryptamine, acetylcholine, endogenous opioids, gamma-aminobutyric acid (GABA), glutamate, and endocannabinoids. The present review examines the limited contribution of the endogenous opioid system to the complex effects of nicotine/tobacco smoking. PMID:18215788

  3. A population-based twin study of the genetic and environmental relationship of major depression, regular tobacco use and nicotine dependence

    PubMed Central

    Edwards, A. C.; Maes, H. H.; Pedersen, N. L.; Kendler, K. S.

    2010-01-01

    Background Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically informative design to assess whether these traits share a common genetic and/or environmental liability. Method We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU. Results The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD–RU and MD–ND relationships are partially attributable to genetic and unique environmental correlations. Conclusions The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate. PMID:20406522

  4. 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. PMID:26886210

  5. α4β2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief.

    PubMed

    McGranahan, Tresa M; Patzlaff, Natalie E; Grady, Sharon R; Heinemann, Stephen F; Booker, T K

    2011-07-27

    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 α4β2-nAChR, endogenously modulates neuronal excitability and thereby, modifies certain normal as well as nicotine-induced behaviors. Although α4-containing nAChRs are widely expressed across the brain, a major focus has been on their roles within midbrain dopaminergic regions involved in drug addiction, mental illness, and movement control in humans. We developed a unique model system to examine the role of α4-nAChRs within dopaminergic neurons by a targeted genetic deletion of the α4 subunit from dopaminergic neurons in mice. The loss α4 mRNA and α4β2-nAChRs from dopaminergic neurons was confirmed, as well as selective loss of α4β2-nAChR function from dopaminergic but not GABAergic neurons. Two behaviors central to nicotine dependence, reward and anxiety relief, were examined. α4-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. α4-nAChRs are necessary for the anxiolytic effects of nicotine in the elevated plus maze, and elimination of α4β2-nAChRs specifically from dopaminergic neurons decreased sensitivity to the anxiolytic effects of nicotine. Deletion of α4-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-related behaviors. PMID:21795541

  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. 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

  9. 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…

  10. 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…

  11. 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

  12. 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

  13. 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. PMID:27233215

  14. Age differences in conditioned place preferences and taste aversions to nicotine.

    PubMed

    Dannenhoffer, Carol A; Spear, Linda P

    2016-07-01

    Adolescents and adults differ in their behavioral sensitivities to drugs of abuse, including nicotine. Studies have shown that both rewarding and aversive properties of drugs of abuse can exist concomitantly. The present study investigated the ontogeny of these opposing qualities across a range of doses using a combined conditioned taste aversion and place preference paradigm in pair-housed rats that were not deprived of food or water. Results indicated that adolescents were more sensitive to the rewarding properties of nicotine than adults. In contrast, although all doses produced a taste aversion at both ages in the same rats, the aversion was weaker at lower than high doses in adolescents whereas adults showed strong aversion at all doses, suggesting modest attenuation in nicotine's aversive properties among adolescents relative to adults. Thus, attenuated aversive and accented appetitive sensitivities of adolescents to nicotine can be experienced simultaneously in the same animals. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 660-666, 2016. PMID:27027859

  15. Decaffeinated coffee and nicotine-free tobacco provide neuroprotection in Drosophila models of Parkinson's disease through an NRF2-dependent mechanism.

    PubMed

    Trinh, Kien; Andrews, Laurie; Krause, James; Hanak, Tyler; Lee, Daewoo; Gelb, Michael; Pallanck, Leo

    2010-04-21

    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

  16. 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

  17. 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.

  18. 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.

  19. Age-Related Differences in the Disposition of Nicotine and Metabolites in Rat Brain and Plasma

    PubMed Central

    2013-01-01

    Introduction: Studies have evaluated the behavioral and neurochemical impact of nicotine administration in rodents. However, the distribution of nicotine and metabolites in rat brain and plasma as a function of age has not been investigated. This is a significant issue because human adolescents have a greater risk for developing nicotine addiction than adults, and reasons underlying this observation have not been fully determined. Thus, in this present study, we evaluated the impact of the transition from adolescence (postnatal day [PND 40]) to adulthood (PND 90) on nicotine distribution in rats. Methods: PND 40, 60, and 90 rats received a single injection of (−) nicotine (0.8mg/kg, subcutaneously). Liquid chromatography tandem-mass spectrometry was used to measure concentration of nicotine and metabolites in selected biological matrices. Results: Nicotine, cotinine, and nornicotine were detected in rat striata and frontal cortex 30min, 1hr, 2hr, and 4hr after a single administration. These and several additional metabolites (nicotine-1′-oxide, cotinine-N-oxide, norcotinine, and trans-3′-hydroxycotinine) were also detected in plasma at these same timepoints. The mean concentration of nicotine in brain and plasma was lower in PND 40 versus PND 90 rats. In contrast, the mean concentration of nornicotine was higher in the plasma and brain of PND 40 versus PND 90 rats. Conclusions: Nicotine and metabolite distribution differs between adolescent and adult rats. These data suggest that adolescent rats metabolize nicotine to some metabolites faster than adult rats. Further studies are needed to investigate the potential correlation between age, drug distribution, and nicotine addiction. PMID:23737496

  20. 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

  1. 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.…

  2. In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects.

    PubMed

    Zorin, S; Kuylenstierna, F; Thulin, H

    1999-08-01

    Permeability tests with Franz' diffusion cells and an in vitro test model were made to evaluate the importance of dermal absorption of nicotine as a pathway for intoxication. Studies were carried out to ensure that safety procedures, when spilling nicotine on skin, are sufficient to prevent poisoning. Pure nicotine and nicotine in various concentrations in water or ethanol were applied on human skin or gloves in Franz' cells. Washing was simulated by removing nicotine from skin after 3 or 5 min. Permeation rate (flux) and lag time were calculated and estimated for human skin. Different glove materials were tested for their nicotine breakthrough time. Flux depended on concentration in a non-linear way when nicotine-water solutions were tested. Highest flux was found in 50% w/w nicotine dissolved in water. Solutions with low concentration of nicotine (1% w/w) dissolved in water had a similar permeation rate to 100% nicotine. Flux was found to be low when using ethanol as a vehicle; flux was also pH-dependent. The nicotine-water solution containing acetic acid had the lowest flux. The tests where nicotine was washed away revealed that skin served as a possible nicotine depot, because nicotine concentration in the receptor compartment continued to increase after removing the nicotine from the surface. The length of contact time affected the amount of substance passing the skin, resulting in great difference between 3 and 5 min contact time, 5 min giving higher nicotine concentration and 3 min lower. This emphasizes the importance of washing away nicotine spilled on skin rapidly. Two glove types were tested and they were found to be appropriate in their use with nicotine if changed regularly. PMID:10518466

  3. Harmful effects of nicotine

    PubMed Central

    Mishra, Aseem; Chaturvedi, Pankaj; Datta, Sourav; Sinukumar, Snita; Joshi, Poonam; Garg, Apurva

    2015-01-01

    With the advent of nicotine replacement therapy, the consumption of the nicotine is on the rise. Nicotine is considered to be a safer alternative of tobacco. The IARC monograph has not included nicotine as a carcinogen. However there are various studies which show otherwise. We undertook this review to specifically evaluate the effects of nicotine on the various organ systems. A computer aided search of the Medline and PubMed database was done using a combination of the keywords. All the animal and human studies investigating only the role of nicotine were included. Nicotine poses several health hazards. There is an increased risk of cardiovascular, respiratory, gastrointestinal disorders. There is decreased immune response and it also poses ill impacts on the reproductive health. It affects the cell proliferation, oxidative stress, apoptosis, DNA mutation by various mechanisms which leads to cancer. It also affects the tumor proliferation and metastasis and causes resistance to chemo and radio therapeutic agents. The use of nicotine needs regulation. The sale of nicotine should be under supervision of trained medical personnel. PMID:25810571

  4. Harmful effects of nicotine.

    PubMed

    Mishra, Aseem; Chaturvedi, Pankaj; Datta, Sourav; Sinukumar, Snita; Joshi, Poonam; Garg, Apurva

    2015-01-01

    With the advent of nicotine replacement therapy, the consumption of the nicotine is on the rise. Nicotine is considered to be a safer alternative of tobacco. The IARC monograph has not included nicotine as a carcinogen. However there are various studies which show otherwise. We undertook this review to specifically evaluate the effects of nicotine on the various organ systems. A computer aided search of the Medline and PubMed database was done using a combination of the keywords. All the animal and human studies investigating only the role of nicotine were included. Nicotine poses several health hazards. There is an increased risk of cardiovascular, respiratory, gastrointestinal disorders. There is decreased immune response and it also poses ill impacts on the reproductive health. It affects the cell proliferation, oxidative stress, apoptosis, DNA mutation by various mechanisms which leads to cancer. It also affects the tumor proliferation and metastasis and causes resistance to chemo and radio therapeutic agents. The use of nicotine needs regulation. The sale of nicotine should be under supervision of trained medical personnel. PMID:25810571

  5. Age-dependency of posture parameters in children and adolescents

    PubMed Central

    Ludwig, Oliver; Mazet, Carola; Mazet, Dirk; Hammes, Annette; Schmitt, Eduard

    2016-01-01

    [Purpose] Poor posture in children and adolescents is a well-known problem. Therefore, early detection of incorrect posture is important. Photometric posture analysis is a cost-efficient and easy method, but needs reliable reference values. As children’s posture changes as they grow, the assessment needs to be age-specific. This study aimed to investigate the development of both one-dimensional posture parameter (body inclination angle) and complex parameter (posture index) in different age groups (childhood to adolescence). [Subjects and Methods] The participants were 372 symptom-free children and adolescents (140 girls and 232 boys aged 6–17). Images of their habitual posture were obtained in the sagittal plane. High-contrast marker points and marker spheres were placed on anatomical landmarks. Based on the marker points, the body inclination angle (INC) and posture index (PI) were calculated using the Corpus concepts software. [Results] The INC angle significantly increased with age. The PI did not change significantly among the age groups. No significant differences between the corresponding age groups were found for PI and INC for both sexes. [Conclusion] When evaluating posture using the body inclination angle, the age of the subject needs to be considered. Posture assessment with an age-independent parameter may be more suitable. PMID:27313382

  6. 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. PMID:25790020

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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. PMID:27059334

  12. Genetic and Pharmacokinetic Determinants of Response to Transdermal Nicotine in White, Black and Asian Non-Smokers

    PubMed Central

    Dempsey, Delia A.; St Helen, Gideon; Jacob, Peyton; Tyndale, Rachel F.; Benowitz, Neal L.

    2013-01-01

    The aim of the study was to examine genetic, pharmacokinetic and demographic factors that influence sensitivity to nicotine in never smokers. Sixty never smokers, balanced for gender and race (Caucasian, Blacks and Asian), wore 7 mg nicotine skin patches for up to 8 hours. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in 9 subjects and was strongly associated with rate of rise and peak concentrations of plasma nicotine. Toxicity, subjective and cardiovascular effects of nicotine were associated with the presence of reduced function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when the latter are used for treating medical conditions in non-smokers, and possibly in vulnerability to developing nicotine dependence. PMID:23933970

  13. 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

  14. 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

  15. 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…

  16. 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

  17. Cellular Basis for the Olfactory Response to Nicotine

    PubMed Central

    2010-01-01

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (RoseJ. E., et al. (1993) Pharmacol., Biochem. Behav.1 (3), 891−9008469698). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (MombaertsP. (1999) Annu. Rev. Neurosci.1, 487−50910202546), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (GomezG., et al. (2000) J. Neurosci. Res.1 (3), 737−74911104513), and rat olfactory neurons. Rat and human OSNs responded to S(−)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID:22777075

  18. Cellular basis for the olfactory response to nicotine.

    PubMed

    Bryant, Bruce; Xu, Jiang; Audige, Valery; Lischka, Fritz W; Rawson, Nancy E

    2010-03-17

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID:22777075

  19. 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

  20. A two-injection protocol for nicotine sensitization.

    PubMed

    Bernardi, Rick E; Spanagel, Rainer

    2014-12-15

    Sensitization to the locomotor activating effect of drugs of abuse occurs following repeated exposure to a drug, and/or when limited exposure to a drug is paired with a specific environment. Conditioned, or context-dependent, sensitization has been well-characterized using limited exposure protocols in, for example, cocaine- and amphetamine-treated animals. However, little data exists regarding limited exposure protocols for other drugs of abuse, such as nicotine. The current experiment investigated whether a two-injection protocol of nicotine administration would result in locomotor sensitization. Mice administered two injections of nicotine (0.175mg/kg, s.c.) 7d apart demonstrated significant locomotor sensitization in response to the second exposure. Furthermore, the development of this sensitization was blocked by the administration of the nicotinic acetylcholine receptor antagonist mecamylamine (2mg/kg) prior to the first nicotine exposure. In a follow-up study, we found that this two-injection nicotine sensitization was independent of context, as separate groups of mice given an initial nicotine exposure (0.175mg/kg, s.c.) in either the specific environment in which locomotor activity was tested or in their home cages demonstrated equivalent levels of locomotor activity during subsequent testing 7d later. These data suggest a novel approach to nicotine sensitization using limited nicotine exposure. PMID:25192633

  1. 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. PMID:9606918

  2. 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. PMID:25180451

  3. Adolescent inpatient girls’ report of dependent life events predicts prospective suicide risk

    PubMed Central

    Stone, Lindsey Beth; Liu, Richard; Yen, Shirley

    2014-01-01

    Adolescents with a history of suicidal behavior are especially vulnerable for future suicide attempts, particularly following discharge from an inpatient psychiatric admission. This study is the first to test whether adolescents’ tendency to generate stress, or report more dependent events to which they contributed, was predictive of prospective suicide events. Ninety adolescent psychiatric inpatients who were admitted for recent suicide risk, completed diagnostic interviews, assessments of history of suicidal behavior, and a self-report questionnaire of major life events at baseline. Participants were followed over the subsequent 6 months after discharge to assess stability vs. onset of suicide events. Cox proportional hazard regressions were used to predict adolescents’ time to suicide events. Results supported hypothesis, such that only recent greater dependent events, not independent or overall events, predicted risk for prospective suicide events. This effect was specific to adolescent girls. Importantly, dependent events maintained statistical significance as a predictor of future suicide events after co-varying for the effects of several established risk factors and psychopathology. Results suggest that the tendency to generate dependent events may contribute unique additional prediction for adolescent girls’ prospective suicide risk, and highlight the need for future work in this area. PMID:24893759

  4. 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…

  5. Noribogaine reduces nicotine self-administration in rats

    PubMed Central

    Chang, Qing; Hanania, Taleen; Mash, Deborah C

    2015-01-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  6. Noribogaine reduces nicotine self-administration in rats.

    PubMed

    Chang, Qing; Hanania, Taleen; Mash, Deborah C; Maillet, Emeline L

    2015-06-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats' levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  7. Effects of a Selective Cannabinoid CB2 Agonist and Antagonist on Intravenous Nicotine Self Administration and Reinstatement of Nicotine Seeking

    PubMed Central

    Gamaleddin, Islam; Zvonok, Alexander; Makriyannis, Alexandros; Goldberg, Steven R.; Le Foll, Bernard

    2012-01-01

    Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2) have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio) and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg) and CB2 agonist AM1241 (1 to 10 mg/kg) on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior. PMID:22291896

  8. 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. PMID:26806777

  9. 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…

  10. Implicit Motivational Processes Underlying Smoking in American and Dutch Adolescents

    PubMed Central

    Larsen, Helle; Kong, Grace; Becker, Daniela; Cousijn, Janna; Boendermaker, Wouter; Cavallo, Dana; Krishnan-Sarin, Suchitra; Wiers, Reinout

    2014-01-01

    Introduction: Research demonstrates that cognitive biases toward drug-related stimuli are correlated with substance use. This study aimed to investigate differences in cognitive biases (i.e., approach bias, attentional bias, and memory associations) between smoking and non-smoking adolescents in the US and the Netherlands. Within the group of smokers, we examined the relative predictive value of the cognitive biases and impulsivity related constructs (including inhibition skills, working memory, and risk taking) on daily smoking and nicotine dependence. Method: A total of 125 American and Dutch adolescent smokers (n = 67) and non-smokers (n = 58) between 13 and 18 years old participated. Participants completed the smoking approach–avoidance task, the classical and emotional Stroop task, brief implicit associations task, balloon analog risk task, the self-ordering pointing task, and a questionnaire assessing level of nicotine dependence and smoking behavior. Results: The analytical sample consisted of 56 Dutch adolescents (27 smokers and 29 non-smokers) and 37 American adolescents (19 smokers and 18 non-smokers). No differences in cognitive biases between smokers and non-smokers were found. Generally, Dutch adolescents demonstrated an avoidance bias toward both smoking and neutral stimuli whereas the American adolescents did not demonstrate a bias. Within the group of smokers, regression analyses showed that stronger attentional bias and weaker inhibition skills predicted greater nicotine dependence while weak working memory predicted more daily cigarette use. Conclusion: Attentional bias, inhibition skills, and working memory might be important factors explaining smoking in adolescence. Cultural differences in approach–avoidance bias should be considered in future research. PMID:24904435

  11. Undetected Ultracet™ dependence in an adolescent with nonmalignant back pain.

    PubMed

    Khan, Nabil A; Sullivan, Maria A; Vitale, Michael G; Tresgallo, Mary Ellen; Saroyan, John M

    2013-01-01

    Addiction to painkillers or other substances in pediatric and adolescent cases of noncancer chronic pain is an understudied phenomenon, even amidst documented increases in rates of prescription opioid use and misuse. Case studies can inform the training of clinicians in ethically negotiating a balance between optimizing analgesia and mitigating risk of aberrant drug-taking behaviors. This report discusses an 18-year-old woman with idiopathic scoliosis and clinical depression secondary to undertreated refractory chronic back pain who underwent surgery to correct pseudoarthrosis after a prior spinal instrumentation operation. This intervention in conjunction with a course of patient-controlled analgesia, hydromorphone, and outpatient tramadol, naproxen, methadone, and gabapentin was successful in addressing her long-standing lumbar pain. The patient, however, continued to complain to her pain management team of postsurgical discomfort and insisted on being prescribed Ultracet™ (acetaminophen-tramadol) rather than generic tramadol. The patient's eventual disclosure of severe withdrawal discomfort and history of covert abuse of Ultracet™ is discussed with respect to key warning signs, gaps, and contingencies in the screening, surgical, and pain management processes. PMID:23771572

  12. 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.

  13. Hormone-dependent adolescent organization of socio-sexual behaviors in mammals.

    PubMed

    Sisk, Cheryl L

    2016-06-01

    The adolescent transition from childhood to adulthood requires both reproductive and behavioral maturation as individuals acquire the ability to procreate. Gonadal steroid hormones are key players in the maturation of behaviors required for reproductive success. Beyond activating behavior in adulthood, testicular and ovarian hormones organize the adolescent brain and program adult-typical and sex-typical expression of sociosexual behaviors. Testicular hormones organize sexual and agonistic behaviors, including social proficiency-the ability to adapt behavior as a function of social experience. Ovarian hormones organize behaviors related to energy balance and maternal care. These sex differences in the behaviors that are programmed by gonadal hormones during adolescence suggest that evolution has selected for hormone-dependent sex-specific organization of behaviors that optimize reproductive fitness. PMID:26963894

  14. 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

  15. Nicotine and health.

    PubMed

    2014-07-01

    Nicotine, an alkaloid derived from the leaves of tobacco plants (Nicotiana tabacum and Nicotiana rustica) is the primary addictive agent in tobacco products.(1,2) There are different ways of administering the various products including smoking cigarettes, chewing tobacco, holding moist snuff in the mouth, inhaling dry snuff through the nose, inhaling smoke from a waterpipe and inhaling vapour from an electronic cigarette.(3-6) It can be difficult differentiating the effects of nicotine from the many other toxic substances these products also contain. Here we review the pharmacological effects of nicotine but we will not review the well-known harmful effects of cigarettes, where it is primarily the toxins and carcinogens in tobacco smoke rather than the nicotine that cause illness and death.(7) A future article will consider the use of electronic cigarettes. PMID:25012148

  16. Republished: Nicotine and health.

    PubMed

    2014-01-01

    Nicotine, an alkaloid derived from the leaves of tobacco plants (Nicotiana tabacum and Nicotiana rustica) is the primary addictive agent in tobacco products.(1,2) There are different ways of administering the various products including smoking cigarettes, chewing tobacco, holding moist snuff in the mouth, inhaling dry snuff through the nose, inhaling smoke from a waterpipe and inhaling vapour from an electronic cigarette.(3-6) It can be difficult differentiating the effects of nicotine from the many other toxic substances these products also contain. Here we review the pharmacological effects of nicotine but we will not review the well-known harmful effects of cigarettes, where it is primarily the toxins and carcinogens in tobacco smoke rather than the nicotine that cause illness and death.(7) A future article will consider the use of electronic cigarettes. PMID:25428425

  17. Nicotine Oral Inhalation

    MedlinePlus

    ... class of medications called smoking cessation aids. It works by providing nicotine to your body to decrease ... want to try different schedules to see what works best for you.Ask your pharmacist or doctor ...

  18. Nicotine replacement therapy

    MedlinePlus

    ... come in many forms: Gum Inhalers Lozenges Nasal spray Skin patch All of these work well if ... inhaler and patch together when quitting. Nicotine Nasal Spray The nasal spray provides a quick dose of ...

  19. Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice.

    PubMed

    O'Rourke, Kyu Y; Touchette, Jillienne C; Hartell, Elizabeth C; Bade, Elizabeth J; Lee, Anna M

    2016-10-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. PMID:27342124

  20. A Randomized Trial of Contingency Management for Adolescent Marijuana Abuse and Dependence

    PubMed Central

    Stanger, Catherine; Budney, Alan J.; Kamon, Jody L.; Thostensen, Jeff

    2009-01-01

    An initial efficacy test of an innovative behavioral outpatient treatment model for adolescents with problematic use of marijuana enrolled 69 adolescents, aged 14–18, and randomly assigned them to one of two treatment conditions. Both conditions received individualized Motivational Enhancement and Cognitive Behavioral Therapy (MET/CBT) and a twice-weekly drug-testing program. The experimental contingency management condition involved a clinic delivered, abstinence-based incentive program, and weekly behavioral parent training sessions that included a parent-delivered, abstinence-based, substance monitoring contract. The comparison condition included an attendance-based incentive program, and weekly psychoeducational parent sessions. Follow-up assessments were performed at 3, 6, 9 months post-treatment. The experimental condition showed greater marijuana abstinence during treatment, e.g., 7.6 vs. 5.1 continuous weeks and 50% vs. 18% achieved ≥ 10 weeks of abstinence. Improvements were found in parenting and youth psychopathology across treatment conditions, and improvements in negative parenting uniquely predicted post treatment abstinence. The outcomes observed in the experimental condition are consistent with adult substance dependence treatment literature, and suggest that integrating CM abstinence-based approaches with other empirically-based outpatient interventions provides an alternative and efficacious treatment model for adolescent substance abuse/dependence. Replication and continued development of more potent interventions remain needed to further advance the development of effective substance abuse treatments for adolescents. PMID:19717250

  1. Emotion recognition specialization and context-dependent risk of anxiety and depression in adolescents

    PubMed Central

    Oldehinkel, Albertine J; Hartman, Catharina A; Van Oort, Floor V A; Nederhof, Esther

    2015-01-01

    Background Some adolescents function poorly in apparently benign environments, while others thrive despite hassles and difficulties. The aim of this study was to examine if adolescents with specialized skills in the recognition of either positive or negative emotions have a context-dependent risk of developing an anxiety or depressive disorder during adolescence, depending on exposure to positive or harsh parenting. Methods Data came from a large prospective Dutch population study (N = 1539). At age 11, perceived parental rejection and emotional warmth were measured by questionnaire, and emotion recognition skills by means of a reaction-time task. Lifetime diagnoses of anxiety and depressive disorders were assessed at about age 19, using a standardized diagnostic interview. Results Adolescents who were specialized in the recognition of positive emotions had a relatively high probability to develop an anxiety disorder when exposed to parental rejection (Bspecialization*rejection = 0.23, P < 0.01) and a relatively low probability in response to parental emotional warmth (Bspecialization*warmth = −0.24, P = 0.01), while the opposite pattern was found for specialists in negative emotions. The effect of parental emotional warmth on depression onset was likewise modified by emotion recognition specialization (B = −0.13, P = 0.03), but the effect of parental rejection was not (B = 0.02, P = 0.72). In general, the relative advantage of specialists in negative emotions was restricted to fairly uncommon negative conditions. Conclusions Our results suggest that there is no unequivocal relation between parenting behaviors and the probability to develop an anxiety or depressive disorder in adolescence, and that emotion recognition specialization may be a promising way to distinguish between various types of context-dependent reaction patterns. PMID:25642389

  2. A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans.

    PubMed

    Saylor, Kyle; Zhang, Chenming

    2016-09-15

    Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. PMID:27473014

  3. Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats

    PubMed Central

    Harris, Andrew C.; Mattson, Christina; LeSage, Mark G.; Keyler, Daniel E.; Pentel, Paul R.

    2010-01-01

    Animal models of tobacco dependence typically rely on parenteral administration of pure nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. The primary goal of this study was to validate methods for administering cigarette smoke to rats using exposure conditions that were clinically relevant and also produced brain nicotine levels similar to those produced by behaviorally active doses of pure nicotine. A secondary goal was to begin examining the behavioral effects of smoke. Nose-only exposure (NOE) to smoke for 10–45 min or whole-body exposure (WBE) to smoke for 1–4 hr produced serum nicotine concentrations similar to those in smokers (14–55 ng/ml), without excessive carbon monoxide exposure. Daily nicotine (0.1 mg/kg, s.c.) induced locomotor sensitization whereas 45-min NOE producing brain nicotine levels within the same range did not. Nicotine 0.125 mg/kg s.c. reversed withdrawal from a chronic nicotine infusion as measured by elevations in intracranial self-stimulation thresholds whereas 4-hr WBE producing similar brain nicotine levels did not. These data demonstrate the feasibility of delivering cigarette smoke to rats at clinically relevant doses, and provide preliminary evidence that the behavioral effects of nicotine delivered in smoke may differ from those of pure nicotine. PMID:20494826

  4. 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. PMID:26774337

  5. 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

  6. Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior

    PubMed Central

    Plaza-Zabala, Ainhoa; Martín-García, Elena; de Lecea, Luis; Maldonado, Rafael; Berrendero, Fernando

    2010-01-01

    Emerging evidence suggests that the hypocretinergic system is involved in addictive behavior. In this study, we investigated the role of these hypothalamic neuropeptides in anxiety-like responses of nicotine and stress-induced reinstatement of nicotine-seeking behavior. Acute nicotine (0.8 mg/kg, sc) induced anxiogenic-like effects in the elevated plus-maze and activated the paraventricular nucleus of the hypothalamus (PVN) as revealed by c-Fos expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 or prepro-hypocretin gene deletion blocked both nicotine effects. In the PVN, SB334867 also prevented the activation of corticotrophin releasing factor (CRF) and arginine-vasopressin (AVP) neurons, which expressed Hcrtr-1. In addition, an increase of the percentage of c-Fos positive hypocretin cells in the perifornical and dorsomedial hypothalamic (PFA/DMH) areas was found after nicotine (0.8 mg/kg, sc) administration. Intracerebroventricular (icv) infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 μl) or footshock stress reinstated a previously extinguished nicotine-seeking behavior. The effects of Hcrt-1 were blocked by SB334867, but not by the CRF1 receptor antagonist antalarmin. Moreover, SB334867 did not block CRF-dependent footshock-induced reinstatement of nicotine-seeking while antalarmin was effective in preventing this nicotine motivational response. Therefore, the Hcrt system interacts with CRF and AVP neurons in the PVN and modulates the anxiogenic-like effects of nicotine whereas Hcrt and CRF play a different role in the reinstatement of nicotine-seeking. Indeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF activation whereas CRF mediates the reinstatement induced by stress. PMID:20147556

  7. Nicotine replacement therapies: patient safety and persistence

    PubMed Central

    Ferguson, Stuart G; Shiffman, Saul; Gitchell, Joseph G

    2011-01-01

    Nicotine replacement therapy (NRT) has become a central part of the treatment of nicotine dependence. However, NRT’s potential efficacy is limited to some extent by patient adherence and persistence. Here we review the relationship between NRT compliance and adherence, and overall treatment outcome. We then examine the factors that likely impact on treatment compliance and persistence, with a special focus on users’ perceptions of treatment safety and efficacy as possible mediators. Potential clinical strategies for improving suboptimal medication use are also discussed. PMID:22915971

  8. 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…

  9. 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. PMID:16737396

  10. PERSONALITY PREDISPOSITIONS IN CHINESE ADOLESCENTS: THE RELATION BETWEEN SELF-CRITICISM, DEPENDENCY, AND PROSPECTIVE INTERNALIZING SYMPTOMS

    PubMed Central

    Cohen, Joseph R.; Young, Jami F.; Hankin, Benjamin L.; Yao, Shuqiao; Zhu, Xiong Zhao; Abela, John R.Z.

    2015-01-01

    The present study examined the prospective relation between two personality predispositions, self-criticism and dependency, and internalizing symptoms. Specifically, it was examined whether self-criticism and dependency predicted symptoms of depression and social anxiety, and if a moderation (e.g. diathesis-stress) or mediation model best explained the relation between the personality predispositions and emotional distress in Chinese adolescents. Participants included 1,150 adolescents (597 females and 553 males) from mainland China. Participants completed self-report measures of self-criticism, dependency, and neuroticism at baseline, and self-report measures of negative events, depressive symptoms, and social anxiety symptoms once a month for six months. Findings showed that self-criticism predicted depressive symptoms, while dependency predicted social anxiety symptoms. In addition, support was found for a mediation model, as opposed to a moderation model, with achievement stressors mediating the relation between self-criticism and depressive symptoms. Overall, these findings highlight new developmental pathways for the development of depression and social anxiety symptoms in mainland Chinese adolescents. Implications for cross-cultural developmental psychopathology research are discussed. PMID:25798026

  11. The Reinforcement Threshold for Nicotine as a Target for Tobacco Control

    PubMed Central

    Sofuoglu, Mehmet; LeSage, Mark G.

    2012-01-01

    BACKGROUND Cigarette smoking represents an enormous public health problem worldwide that leads to over 5 million deaths per year. The gradual reduction of the nicotine content of cigarettes below the threshold that is required to develop addiction is one strategy that might substantially reduce the number of addicted smokers and prevent adolescents from becoming addicted to nicotine (Benowitz and Henningfield 1994). While the potential public health benefits of this approach are enormous, the guiding concepts and relevant empirical evidence needed to support the implementation of a nicotine reduction policy require a critical examination. METHODS The purpose of this paper is to briefly review the current concepts and research regarding nicotine reduction while also discussing the utility of the addictive threshold for nicotine in this approach. The accurate determination of the nicotine addiction threshold presents some conceptual challenges as there is a lack of consensus on how to best measure nicotine addiction. This difficulty can impede the progress for developing a science-based tobacco control policy. As an alternative, the nicotine reinforcement threshold is a relatively clear concept, and well-accepted methods and criteria are available to measure nicotine reinforcement. RESULTS However, there are many gaps in our current knowledge concerning the nicotine reinforcement threshold in humans. The threshold for nicotine reinforcement remains to be determined in controlled settings using different populations of current or potential tobacco users. In addition, the value of the nicotine reinforcement threshold in predicting tobacco use in real-world settings needs to be examined. The results of such studies will determine the potential utility of the estimated threshold for nicotine reinforcement in developing science-based tobacco control policies. PMID:22622242

  12. The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

    PubMed

    McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

    2016-07-01

    Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. PMID:25904425

  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. PMID:16917946

  14. Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice.

    PubMed

    Moerke, Megan J; de Moura, Fernando B; Koek, Wouter; McMahon, Lance R

    2016-09-01

    Some drugs that are positive allosteric nAChR modulators in vitro, desformylflustrabromine (dFBr), PNU-120596 and LY 2087101, have not been fully characterized in vivo. These drugs were examined for their capacity to share or modify the hypothermic and discriminative stimulus effects of nicotine (1mg/kg s.c.) in male C57Bl/6J mice. Nicotine, dFBr, and PNU-120596 produced significant hypothermia, whereas LY 2087101 (up to 100mg/kg) did not. Nicotine dose-dependently increased nicotine-appropriate responding and decreased response rate; the respective ED50 values were 0.56mg/kg and 0.91mg/kg. The modulators produced no more than 38% nicotine-appropriate responding up to doses that disrupted operant responding. Rank order potency was the same for hypothermia and rate-decreasing effects: nicotine>dFBr>PNU-120596=LY 2087101. Mecamylamine and the α4β2 nAChR antagonist dihydro-β-erythroidine, but not the α7 antagonist methyllycaconitine, antagonized the hypothermic effects of nicotine. In contrast, mecamylamine did not antagonize the hypothermic effects of the modulators. The combined discriminative stimulus effects of DFBr and nicotine were synergistic, whereas the combined hypothermic effects of nicotine with either dFBr or PNU-120596 were infra-additive. PNU-120596 did not modify the nicotine discriminative stimulus, and LY 2087101 did not significantly modify either effect of nicotine. Positive modulation of nicotine at nAChRs by PNU-120596 and LY 2087101 in vitro does not appear to confer enhancement of the nAChR-mediated hypothermic or discriminative stimulus effects of nicotine. However, dFBr appears to be a positive allosteric modulator of some behavioral effects of nicotine at doses of dFBr smaller than the doses producing unwanted effects (e.g. hypothermia) through non-nAChR mechanisms. PMID:27238974

  15. Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics

    PubMed Central

    Gilbertson, Rebecca; Frye, Reginald F.; Nixon, Sara Jo

    2011-01-01

    Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals. PMID:21045074

  16. 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). PMID:21316467

  17. 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

  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. Electronic Cigarettes Are a Source of Thirdhand Exposure to Nicotine

    PubMed Central

    Lee, Lily

    2015-01-01

    Introduction: Substances remaining on the surfaces in areas where people have smoked contribute to thirdhand exposure. Nicotine from tobacco smoke has been shown to react with oxidizing chemicals in the air to form secondary pollutants, such as carcinogenic nitrosamines. While prev ious studies have demonstrated thirdhand exposure to nicotine from tobacco smoke, none have investigated whether nicotine from electronic cigarettes (e-cigarettes) can also be deposited on various surfaces. Methods: Three brands of e-cigarettes were refilled with varying nicotine concentrations. We released 100 puffs from each product directly into an exposure chamber. Surface wipe samples were taken from 5 indoor 100cm2 surfaces (window, walls, floor, wood, and metal) pre- and post-release of vapors. Nicotine was extracted from the wipes and was analyzed using gas chromatography. Results: Three of the 4 experiments showed significant increases in the amount of nicotine on all five surfaces. The floor and glass windows had the greatest increases in nicotine, on average by a factor of 47 and 6, respectively (p < .05). The average amount of nicotine deposited on a floor during each experiment was 205 μg/m2 and varied from limit of quantitation to 550 μg/m2. Conclusions: This study indicates that there is a risk for thirdhand exposure to nicotine from e-cigarettes. Thirdhand exposure levels differ depending on the surface and the e-cigarette brand. Future research should explore the potential risks of thirdhand exposure to carcinogens formed from the nicotine that is released from e-cigarettes. PMID:25173774

  20. Iodine Deficiency in a Parenteral Nutrition-Dependent Adolescent With Intestinal Pseudo-Obstruction.

    PubMed

    Mortensen, Melissa; Williamson, Nila; Davis, Cheryl; Kanyu Hsu, Evelyn; Javid, Patrick J; Horslen, Simon

    2016-07-01

    Routine supplementation of iodine in parenteral nutrition (PN) solutions is not current practice in the United States. In this case study, we describe an incidental finding of goiter in a long-term PN-dependent adolescent. With increased iodine screening, we then identified additional patients with undetectable urinary iodine concentrations in our population of children with short bowel receiving long-term PN. We hypothesize that 2 practice changes are possibly reducing iodine provision to long-term PN-dependent patients: transition to alcohol-based skin preparations and lipid minimization. PMID:25261415

  1. 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

  2. Effects of User Puff Topography, Device Voltage, and Liquid Nicotine Concentration on Electronic Cigarette Nicotine Yield: Measurements and Model Predictions

    PubMed Central

    Talih, Soha; Balhas, Zainab; Eissenberg, Thomas; Salman, Rola; Karaoghlanian, Nareg; El Hellani, Ahmad; Baalbaki, Rima; Saliba, Najat

    2015-01-01

    Introduction: Some electronic cigarette (ECIG) users attain tobacco cigarette–like plasma nicotine concentrations while others do not. Understanding the factors that influence ECIG aerosol nicotine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. Methods: Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3–5.2 V or 3.0–7.5 W) and e-liquid nicotine concentration (18–36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and to provide insight into the empirical observations. Results: Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R 2 = 0.99). Conclusions: Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters. PMID:25187061

  3. Functional Upregulation of α4* Nicotinic Acetylcholine Receptors in VTA GABAergic Neurons Increases Sensitivity to Nicotine Reward

    PubMed Central

    Ngolab, Jennifer; Liu, Liwang; Zhao-Shea, Rubing; Gao, Guangping; Gardner, Paul D.

    2015-01-01

    Chronic nicotine exposure increases sensitivity to nicotine reward during a withdrawal period, which may facilitate relapse in abstinent smokers, yet the molecular neuroadaptation(s) that contribute to this phenomenon are unknown. Interestingly, chronic nicotine use induces functional upregulation of nicotinic acetylcholine receptors (nAChRs) in the mesocorticolimbic reward pathway potentially linking upregulation to increased drug sensitivity. In the ventral tegmental area (VTA), functional upregulation of nAChRs containing the α4 subunit (α4* nAChRs) is restricted to GABAergic neurons. To test the hypothesis that increased functional expression of α4* nAChRs in these neurons modulates nicotine reward behaviors, we engineered a Cre recombinase-dependent gene expression system to selectively express α4 nAChR subunits harboring a “gain-of-function” mutation [a leucine mutated to a serine residue at the 9′ position (Leu9′Ser)] in VTA GABAergic neurons of adult mice. In mice expressing Leu9′Ser α4 nAChR subunits in VTA GABAergic neurons (Gad2VTA:Leu9′Ser mice), subreward threshold doses of nicotine were sufficient to selectively activate VTA GABAergic neurons and elicit acute hypolocomotion, with subsequent nicotine exposures eliciting tolerance to this effect, compared to control animals. In the conditioned place preference procedure, nicotine was sufficient to condition a significant place preference in Gad2VTA:Leu9′Ser mice at low nicotine doses that failed to condition control animals. Together, these data indicate that functional upregulation of α4* nAChRs in VTA GABAergic neurons confers increased sensitivity to nicotine reward and points to nAChR subtypes specifically expressed in GABAergic VTA neurons as molecular targets for smoking cessation therapeutics. PMID:26041923

  4. 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

  5. Degradation Kinetics of Benzyl Nicotinate in Aqueous Solution

    PubMed Central

    Mbah, C. J.

    2010-01-01

    The degradation of benzyl nicotinate in aqueous solution over a pH range of 2.0-10.0 at 50±0.2° was studied. The degradation was determined by high performance liquid chromatography. The degradation was observed to follow apparent first-order rate kinetics and the rate constant for the decomposition at 25° was estimated by extrapolation. The reaction was shown to be hydroxide ion catalyzed and the Arrhenius plots showed the temperature dependence of benzyl nicotinate degradation. A significant increase in the stability of benzyl nicotinate was observed when glycerol or polyethylene glycol 400 was incorporated into the aqueous solution. PMID:20582189

  6. Nicotine increases GABAergic input on rat dorsal raphe serotonergic neurons through alpha7 nicotinic acetylcholine receptor.

    PubMed

    Hernández-Vázquez, F; Chavarría, K; Garduño, J; Hernández-López, S; Mihailescu, S P

    2014-12-15

    The dorsal raphe nucleus (DRN) contains large populations of serotonergic (5-HT) neurons. This nucleus receives GABAergic inhibitory afferents from many brain areas and from DRN interneurons. Both GABAergic and 5-HT DRN neurons express functional nicotinic acetylcholine receptors (nAChRs). Previous studies have demonstrated that nicotine increases 5-HT release and 5-HT DRN neuron discharge rate by stimulating postsynaptic nAChRs and by increasing glutamate and norepinephrine release inside DRN. However, the influence of nicotine on the GABAergic input to 5-HT DRN neurons was poorly investigated. Therefore, the aim of this work was to determine the effect of nicotine on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of 5-HT DRN neurons and the subtype of nAChR(s) involved in this response. Experiments were performed in coronal slices obtained from young Wistar rats. GABAergic sIPSCs were recorded from post hoc-identified 5-HT DRN neurons with the whole cell voltage patch-clamp technique. Administration of nicotine (1 μM) increased sIPSC frequency in 72% of identified 5-HT DRN neurons. This effect was not reproduced by the α4β2 nAChR agonist RJR-2403 and was not influenced by TTX (1 μM). It was mimicked by the selective agonist for α7 nAChR, PNU-282987, and exacerbated by the positive allosteric modulator of the same receptor, PNU-120596. The nicotine-induced increase in sIPSC frequency was independent on voltage-gated calcium channels and dependent on Ca(2+)-induced Ca(2+) release (CICR). These results demonstrate that nicotine increases the GABAergic input to most 5-HT DRN neurons, by activating α7 nAChRs and producing CICR in DRN GABAergic terminals. PMID:25231613

  7. c-Jun-N-terminal kinase 1 is necessary for nicotine-induced enhancement of contextual fear conditioning.

    PubMed

    Leach, Prescott T; Kenney, Justin W; Gould, Thomas J

    2016-08-01

    Acute nicotine enhances hippocampus-dependent learning. Identifying how acute nicotine improves learning will aid in understanding how nicotine facilitates the development of maladaptive memories that contribute to drug-seeking behaviors, help development of medications to treat disorders associated with cognitive decline, and advance understanding of the neurobiology of learning and memory. The effects of nicotine on learning may involve recruitment of signaling through the c-Jun N-terminal kinase family (JNK 1-3). Learning in the presence of acute nicotine increases the transcription of mitogen-activated protein kinase 8 (MAPK8, also known as JNK1), likely through a CREB-dependent mechanism. The functional significance of JNK1 in the effects of acute nicotine on learning, however, is unknown. The current studies undertook a backward genetic approach to determine the functional contribution JNK1 protein makes to nicotine-enhanced contextual fear conditioning. JNK1 wildtype (WT) and knockout (KO) mice were administered acute nicotine prior to contextual and cued fear conditioning. 24h later, mice were evaluated for hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear conditioning) memory. Nicotine selectively enhanced contextual conditioning in WT mice, but not in KO mice. Nicotine had no effect on hippocampus-independent learning in either genotype. JNK1 KO and WT mice given saline showed similar levels of learning. These data suggest that JNK1 may be recruited by nicotine and is functionally necessary for the acute effects of nicotine on learning and memory. PMID:27235579

  8. The effects of extrinsic context on nicotine discrimination.

    PubMed

    Duka, T; Seiss, E; Tasker, R

    2002-02-01

    There is evidence from memory studies that context acquired in parallel with the encoded material will facilitate retrieval. However, relatively little is known of how context affects drug discrimination behaviour in humans. The present study employs conventional drug discrimination procedures to investigate the effects of music, as an external cue, on nicotine drug discrimination. Subjects were trained to discriminate a low dose of nicotine (1 mg) from placebo while listening to two different types of music [elated (EL) and depressant (DE): thought to induce happy and sad mood respectively]. Half of the subjects received EL music with nicotine and DE with placebo and the other half vice versa. At the end of training, subjects who reached the criterion (80% of trials identified correctly) entered the generalization phase and were required to discriminate different doses of nicotine (0, 0.25, 0.5 and 1 mg) by indicating how similar each sample was to the training dose. Generalization took place in the presence of either EL or DE music. Nicotine-appropriate responding during generalization was linearly related to dose, with subjects being able to distinguish 0.5mg of nicotine from placebo. Nicotine-appropriate responding at generalization was higher when the context (type of music) was the same as the one employed during discrimination training when nicotine was administered (i.e. a context-dependent generalization effect was present). In addition, it was shown that the context-dependent effect was due to the properties of the EL music. These data provide the first evidence that extrinsic context can facilitate nicotine discrimination in humans. In addition, the findings suggest that this facilitatory effect is not a general effect but is sensitive to specific attributes of the context. PMID:11990718

  9. Positive allosteric modulation of α4β2 nicotinic acetylcholine receptors as a new approach to smoking reduction: evidence from a rat model of nicotine self-administration

    PubMed Central

    Liu, Xiu

    2013-01-01

    Rationale The α4β2 subtype of nicotinic acetylcholine receptors (nAChRs) plays a central role in the mediation of nicotine reinforcement. Positive allosteric modulators (PAMs) at α4β2 nAChRs facilitate the intrinsic efficiency of these receptors although they do not directly activate the receptors. α4β2 PAMs are hypothesized to reduce nicotine self-administration in subjects engaged in routine nicotine consumption. The present study tested this hypothesis using a rat model of nicotine self-administration. Methods Male Sprague-Dawley rats were trained in daily 1 h sessions to intravenously self-administer nicotine (0.03 mg/kg/infusion, free base) on a fixed-ratio 5 schedule. Effects of the α4β2 PAM desformylflustrabromine (dFBr), α4β2 agonist 5-iodo-A-85380, and acetylcholinesterase inhibitor galantamine on nicotine intake were examined. The ability of dFBr and 5-iodo-A-85380 to substitute for nicotine was also assessed. Results dFBr and 5-iodo-A-85380 dose-dependently reduced nicotine self-administration without changing lever responses for food. Galantamine decreased self-administration of nicotine and food at high doses. Unlike 5-iodo-A-85380, dFBr failed to substitute for nicotine in supporting self-administration behavior. Conclusions These results demonstrated the effectiveness of dFBr in reducing nicotine intake and the inability of dFBr to support self-administration behavior. These findings suggest that positive allosteric modulation of α4β2 nAChRs may be a promising target for the treatment of nicotine addiction. Moreover, α4β2 PAMs, in contrast to agonist medications, may have clinical advantages because they may have little liability for abuse because of their lack of reinforcing actions on their own. PMID:23712602

  10. BEHAVIORAL MECHANISMS UNDERLYING NICOTINE REINFORCEMENT

    PubMed Central

    Rupprecht, Laura E.; Smith, Tracy T.; Schassburger, Rachel L.; Buffalari, Deanne M.; Sved, Alan F.; Donny, Eric C.

    2015-01-01

    Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness. PMID:25638333

  11. Waterpipe tobacco products: nicotine labelling versus nicotine delivery

    PubMed Central

    Vansickel, Andrea R; Shihadeh, Alan; Eissenberg, Thomas

    2013-01-01

    Background Waterpipe tobacco package labelling typically indicates “0.0% tar” and “0.05% or 0.5% nicotine”. Objective To determine the extent to which nicotine labeling is related to nicotine delivery. Methods 110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA. Results Topography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml). Conclusions Nicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a “0.05% nicotine” label led to greater plasma nicotine levels than smoking a brand with a “0.5% nicotine” label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers. PMID:21636612

  12. Effect of nicotine on rectal mucus and mucosal eicosanoids.

    PubMed Central

    Zijlstra, F J; Srivastava, E D; Rhodes, M; van Dijk, A P; Fogg, F; Samson, H J; Copeman, M; Russell, M A; Feyerabend, C; Williams, G T

    1994-01-01

    Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel. PMID:8307477

  13. SENSORY REINFORCEMENT ENHANCING EFFECTS OF NICOTINE VIA SMOKING

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.

    2014-01-01

    As in animal research, acute nicotine in humans 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 (“sensory”) rewards, for monetary (“non-sensory”) reward, 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 three similar experimental sessions, each following overnight abstinence (verified by CO<10 ppm) and varying only in the smoking condition. Sessions involved no smoking or smoking denicotinized (0.05 mg) or nicotine (0.6 mg) QuestR 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 denicotinized cigarette (i.e. nicotine per se), while there were no differences between the denicotinized cigarette versus 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 non-sensory) types of rewards may be more modest. PMID:25180451

  14. Nicotinic receptors in addiction pathways.

    PubMed

    Leslie, Frances M; Mojica, Celina Y; Reynaga, Daisy D

    2013-04-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that consist of pentameric combinations of α and β subunits. These receptors are widely distributed throughout the brain and are highly expressed in addiction circuitry. The role of nAChRs in regulating neuronal activity and motivated behavior is complex and varies both in and among brain regions. The rich diversity of central nAChRs has hampered the characterization of their structure and function with use of classic pharmacological techniques. However, recent molecular approaches using null mutant mice with specific regional lentiviral re-expression, in combination with neuroanatomical and electrophysiological techniques, have allowed the elucidation of the influence of different nAChR types on neuronal circuit activity and behavior. This review will address the influence of nAChRs on limbic dopamine circuitry and the medial habenula-interpeduncular nucleus complex, which are critical mediators of reinforced behavior. Characterization of the mechanisms underlying regulation of addiction pathways by endogenous cholinergic transmission and by nicotine may lead to the identification of new therapeutic targets for treating tobacco dependence and other addictions. PMID:23247824

  15. Nicotinic Receptors in Neurodegeneration

    PubMed Central

    Posadas, Inmaculada; López-Hernández, Beatriz; Ceña, Valentín

    2013-01-01

    Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. PMID:24179465

  16. 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 dependence in adolescence by way of a childhood externalizing pathway and a childhood internalizing pathway. Moreover, we tested whether variation in FK506 binding protein 5 gene (FKBP5) CATT haplotype moderated these pathways. The participants were 326 children (n =179 maltreated; n = 147 nonmaltreated) assessed across two waves of data collection (childhood: ages 7-9 and adolescence: ages 15-18). Results indicated that higher levels of child externalizing symptoms significantly mediated the effect of child maltreatment on adolescent marijuana dependence symptoms for individuals with one or two copies of the FKBP5 CATT haplotype only. We did not find support for an internalizing pathway from child maltreatment to adolescent marijuana dependence, nor did we find evidence of moderation of the internalizing pathway by FKBP5 haplotype variation. Findings extend previous research by demonstrating that whether a maltreated child will traverse an externalizing pathway toward substance use disorder in adolescence is dependent on FKBP5 genetic variation. PMID:26535939

  17. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

    SciTech Connect

    Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A. . E-mail: t.slotkin@duke.edu

    2005-08-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults.

  18. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions.

    PubMed

    Pak, Arlene C; Ashby, Charles R; Heidbreder, Christian A; Pilla, Maria; Gilbert, Jeremy; Xi, Zheng-Xiong; Gardner, Eliot L

    2006-10-01

    Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (CPP). Nicotine was given subcutaneously within the dose range of 0.25-0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1-12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence. PMID:16942635

  19. Varenicline, a Partial Agonist at Neuronal Nicotinic Receptors, Reduces Nicotine-Induced Increases in 20% Ethanol Operant Self-Administration in Sprague-Dawley Rats

    PubMed Central

    Bito-Onon, Jade J.; Simms, Jeffrey A.; Chatterjee, Susmita; Holgate, Joan; Bartlett, Selena E.

    2010-01-01

    Alcohol and nicotine use disorders are often treated as separate diseases, despite evidence that approximately 80–90% of alcohol dependent individuals are also heavy smokers. Both nicotine and ethanol have been shown to interact with neuronal nicotinic acetylcholine receptors (nAChRs), suggesting these receptors are a common biological target for the effects of nicotine and ethanol in the brain. There are few studies that have examined the effects of co-administered nicotine and ethanol on the activity of nAChRs in rodents. In the present study, we show that Sprague-Dawley rats, a strain often used for nicotine studies but not as often for voluntary ethanol intake studies, will consume 20% ethanol using both the intermittent-access two-bottle-choice and operant self-administration models without the need for sucrose fading. We show that nicotine (0.2mg/kg and 0.8mg/kg, s.c.) significantly increases operant 20% ethanol self-administration and varenicline (2mg/kg, s.c), a partial agonist at nAChRs, significantly decreases operant ethanol self-administration and nicotine-induced increases in ethanol self-administration. This suggests that nAChRs play an important role in increasing ethanol self-administration and that varenicline may be an efficacious treatment for alcohol and nicotine co-dependencies. PMID:21392178

  20. Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

    PubMed

    Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

    2015-07-15

    The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation. PMID:25979079

  1. Motoneuron axon pathfinding errors in zebrafish: differential effects related to concentration and timing of nicotine exposure.

    PubMed

    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. PMID:25668718

  2. Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig.

    PubMed

    Donnerer, Josef; Liebmann, Ingrid

    2015-01-01

    In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability. PMID:26088942

  3. Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes

    PubMed Central

    O'Dell, Laura E.; Natividad, Luis A.; Pipkin, Joseph A.; Roman, Francisco; Torres, Ivan; Jurado, Jesus; Torres, Oscar V.; Friedman, Theodore C.; Tenayuca, John M.; Nazarian, Arbi

    2013-01-01

    Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ- versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes. PMID:23834715

  4. Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures

    PubMed Central

    Schweitzer, Kelly S.; Chen, Steven X.; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J.; Hubbard, Walter C.; Kim, Elena S.; Lai, Xianyin; Wang, Mu; Kranz, William D.; Carroll, Clinton J.; Ray, Bruce D.; Bittman, Robert; Goodpaster, John

    2015-01-01

    The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1–20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10–20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation. PMID:25979079

  5. Predictors and Sequelae of Smoking Topography Over the Course of a Single Cigarette in Adolescent Light Smokers

    PubMed Central

    Veilleux, Jennifer C.; Kassel, Jon D.; Heinz, Adrienne J.; Braun, Ashley; Wardle, Margaret C.; Greenstein, Justin; Evatt, Daniel P.; Conrad, Megan

    2011-01-01

    Purpose The objective of this study was to determine whether adolescent smokers, who varied in their smoking histories and symptoms of nicotine dependence, exhibit any decrease in puff volume and duration similar to that typically seen in dependent adolescent and adult smokers. Moreover, we examined whether puffing trajectories were moderated by individual difference factors, as well as whether puffing topography over the course of smoking a single cigarette was predictive of an escalation in dependence symptoms. Methods We assessed smoking topography (puff number, duration, volume, maximum flow rate [velocity], and inter-puff interval) over the course of smoking a single cigarette in a sample of 78 adolescent light smokers, using hierarchical linear modeling. We examined moderators (anxiety, depression, nicotine dependence) of the topographic trajectories, as well as whether smoking topography predicted any change in dependence over a 2-year period. Results Puff volume and puff duration decreased over the course of smoking the cigarette, whereas puff velocity and inter-puff interval increased. Slopes for puff volume and duration were moderated by anxiety and depressive symptoms. Moreover, individuals with a less “typical” topography pattern (exhibited stable or increasing volume and duration over the course of smoking the cigarette) demonstrated a heightened dependence escalation in the subsequent 2 years. Conclusion Our findings suggest that adolescent light smokers self-regulate nicotine during the course of smoking a single cigarette, similar to that reported in dependent adolescent and adult smokers. However, single cigarette self-regulation was influenced by certain affective factors. Implications of these findings and future directions for adolescent smoking research are discussed. PMID:21257117

  6. Alcohol-Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

    PubMed Central

    Palm, Sara; Nylander, Ingrid

    2014-01-01

    Background Endogenous opioids are implicated in the mechanism of action of alcohol and alcohol affects opioids in a number of brain areas, although little is known about alcohol's effects on opioids in the adolescent brain. One concern, in particular when studying young animals, is that alcohol intake models often are based on single housing that may result in alcohol effects confounded by the lack of social interactions. The aim of this study was to investigate short- and long-term alcohol effects on opioids and the influence of housing conditions on these effects. Methods In the first part, opioid peptide levels were measured after one 24-hour session of single housing and 2-hour voluntary alcohol intake in adolescent and adult rats. In the second part, a model with a cage divider inserted during 2-hour drinking sessions was tested and the effects on opioids were examined after 6 weeks of adolescent voluntary intake in single-and pair-housed rats, respectively. Results The effects of single housing were age specific and affected Met-enkephalin-Arg6Phe7 (MEAP) in particular. In adolescent rats, it was difficult to distinguish between effects induced by alcohol and single housing, whereas alcohol-specific effects were seen in dynorphin B (DYNB), beta-endorphin (BEND), and MEAP levels in adults. Voluntary drinking affected several brain areas and the majority of alcohol-induced effects were not dependent on housing. However, alcohol effects on DYNB and BEND in the amygdala were dependent on housing. Housing alone affected MEAP in the cingulate cortex. Conclusions Age-specific housing- and alcohol-induced effects on opioids were found. In addition, prolonged voluntary alcohol intake under different housing conditions produced several alcohol-induced effects independent of housing. However, housing-dependent effects were found in areas implicated in stress, emotionality, and alcohol use disorder. Housing condition and age may therefore affect the reasons and

  7. Modeling nicotine addiction in rats.

    PubMed

    Caille, Stephanie; Clemens, Kelly; Stinus, Luis; Cador, Martine

    2012-01-01

    Among the human population, 15% of drug users develop a pathological drug addiction. This figure increases substantially with nicotine, whereby more than 30% of those who try smoking develop a nicotine addiction. Drug addiction is characterized by compulsive drug-seeking and drug-taking behaviors (craving), and loss of control over intake despite impairment in health, social, and occupational functions. This behavior can be accurately modeled in the rat using an intravenous self-administration (IVSA) paradigm. Initial attempts at establishing nicotine self-administration had been problematic, yet in recent times increasingly reliable models of nicotine self-administration have been developed. The present article reviews different characteristics of the nicotine IVSA model that has been developed to examine nicotine reinforcing and motivational properties in rats. PMID:22231818

  8. Effects of combined nicotine and fluoxetine treatment on adult hippocampal neurogenesis and conditioned place preference.

    PubMed

    Faillace, M P; Zwiller, J; Bernabeu, R O

    2015-08-01

    Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It is known to be induced by antidepressant treatment and reduced in response to nicotine administration. We checked here whether the antidepressant fluoxetine would inverse the decrease in hippocampal neurogenesis caused by nicotine. It is shown that repeated, but not a single injection of rats with fluoxetine was able to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. We measured the expression of several biochemical parameters known to be associated with neurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP than nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were completely abolished in response to repeated fluoxetine injections. Expression of nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP-responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able to disrupt the association between nicotine and the environment, this antidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy. PMID:25981209

  9. Nicotine reinforcement is reduced by cannabinoid CB1 receptor blockade in the ventral tegmental area.

    PubMed

    Simonnet, Amelie; Cador, Martine; Caille, Stephanie

    2013-11-01

    Cannabinoid type 1 (CB1) receptors control the motivational properties and reinforcing effects of nicotine. Indeed, peripheral administration of a CB1 receptor antagonist dramatically decreases both nicotine taking and seeking. However, the neural substrates through which the cannabinoid CB1 receptors regulate the voluntary intake of nicotine remain to be elucidated. In the present study, we sought to determine whether central injections of a CB1 receptor antagonist delivered either into the ventral tegmental area (VTA) or the nucleus accumbens (NAC) may alter nicotine intravenous self-administration (IVSA). Rats were first trained to self-administer nicotine (30 μg/kg/0.1 ml). The effect of central infusions of the CB1 antagonist AM 251 (0, 1 and 10 μg/0.5 μl/side) on nicotine-taking behavior was then tested. Intra-VTA infusions of AM 251 dose dependently reduced IVSA with a significant decrease for the dose 10 μg/0.5 μl/side. Moreover, operant responding for water was unaltered by intra-VTA AM 251 at the same dose. Surprisingly, intra-NAC delivery of AM 251 did not alter nicotine behavior at all. These data suggest that in rats chronically exposed to nicotine IVSA, the cannabinoid CB1 receptors located in the VTA rather than in the NAC specifically control nicotine reinforcement and, subsequently, nicotine-taking behavior. PMID:22784230

  10. A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence.

    PubMed

    Stallings, Michael C; Corley, Robin P; Hewitt, John K; Krauter, Kenneth S; Lessem, Jeffrey M; Mikulich, Susan K; Rhee, Soo Hyun; Smolen, Andrew; Young, Susan E; Crowley, Thomas J

    2003-06-01

    This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838). PMID:12757967

  11. Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

    PubMed

    Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2015-05-01

    Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. PMID:25744879

  12. Nicotine effect on cardiovascular system and ion channels.

    PubMed

    Hanna, Salma Toma

    2006-03-01

    Smoking is a leading cause of cardiovascular disease, hypertension, myocardial infarction, and stroke. Nicotine is one of the components of cigarette smoke. Nicotine effects on the cardiovascular system reflect the activity of the nicotine receptors centrally and on peripheral autonomic ganglia. It has been found that cigarette smoke extract-induced contraction of porcine coronary arteries is related to superoxide anion-mediated degradation of nitric oxide. Treatment of rabbit aortas with an oxygen free radicals scavenger attenuated cigarette smoke impairment of arterial relaxation. Treatment of smokers with vitamin C, an antioxidant, improved impaired endothelium-dependent reactivity of large peripheral arteries. Thus it appears that chronic smoking and acute exposure to cigarette smoke extract may alter endothelium-dependent reactivity via the production of oxygen derived free radicals. This review discusses the effects of nicotine on resistance arterioles, compliance arteries, smooth muscle cells, and ion channels in the cardiovascular system. We discuss studies performed on humans, nicotine-exposed animals, and cell cultures yielding varying and inconsistent results that may be due to differences in experimental design, species, and the dose of exposure. Nicotine exposure appears to induce a combination of free radical production, vascular wall adhesion, and a reduction of fibrinolytic activity in the plasma. PMID:16633075

  13. The future of nicotine replacement.

    PubMed

    Russell, M A

    1991-05-01

    Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether. PMID:1859935

  14. Nicotine and periodontal tissues

    PubMed Central

    Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Kaushal, Sumit

    2010-01-01

    Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment, alveolar bone and a higher rate of tooth loss. Nicotine, a major component and most pharmacologically active agent in tobacco is likely to be a significant contributing factor for the exacerbation of periodontal diseases. Available literature suggests that nicotine affects gingival blood flow, cytokine production, neutrophil and other immune cell function; connective tissue turnover, which can be the possible mechanisms responsible for overall effects of tobacco on periodontal tissues. Inclusion of tobacco cessation as a part of periodontal therapy encourages dental professionals to become more active in tobacco cessation counseling. This will have far reaching positive effects on our patients’ oral and general health. PMID:20922084

  15. Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors

    PubMed Central

    Timmermann, DB; Sandager-Nielsen, K; Dyhring, T; Smith, M; Jacobsen, A-M; Nielsen, EØ; Grunnet, M; Christensen, JK; Peters, D; Kohlhaas, K; Olsen, GM; Ahring, PK

    2012-01-01

    BACKGROUND AND PURPOSE Positive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH Effects of NS9283 were evaluated in vitro using fluorescence-based Ca2+ imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats. KEY RESULTS NS9283 was shown to increase agonist-evoked response amplitude of (α4)3(β2)2 nACh receptors in electrophysiology paradigms. (α2)3(β2)2, (α2)3(β4)2 and (α4)3(β4)2 were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3β stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHβE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors. CONCLUSIONS AND IMPLICATIONS These results provide compelling evidence that positive allosteric modulators acting at the (α4)3(β2)2 nACh receptors can augment activity across a broad range of cognitive domains, and that α4β2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment. PMID:22506660

  16. Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

    PubMed

    Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

    2016-07-01

    Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration. PMID:26717881

  17. Estrogen provokes the depressant effect of chronic nicotine on vagally mediated reflex chronotropism in female rats.

    PubMed

    El-Mas, Mahmoud M; El-Gowelli, Hanan M; El-Gowilly, Sahar M; Fouda, Mohamed A; Helmy, Mai M

    2012-08-01

    We recently reported that acute nicotine impairs reflex tachycardic activity in estrogen-depleted, but not estrogen-repleted, female rats, suggesting a restraining influence for estrogen against the nicotine effect. In this study, we tested whether the baroreflex-protective effect of estrogen can be replicated when nicotine was administered chronically. We also report on the dose dependence and autonomic modulation of the nicotine-baroreflex interaction. The effects of nicotine (0.5, 1, or 2 mg/kg/day for 14 days) on baroreflex curves relating changes in heart rate to increases [phenylephrine (PE)] or decreases [sodium nitroprusside (SNP)] in blood pressure were evaluated in sham-operated (SO), ovariectomized (OVX), and estrogen-replaced OVX (OVXE(2)) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(SNP)). In SO rats, both reflex bradycardic and tachycardic responses were attenuated by nicotine in a dose-related fashion. In nicotine-treated rats, blockade of β-adrenergic (propranolol), but not muscarinic (atropine), receptors caused additional reductions in reflex chronotropic responses, implying that nicotine selectively impairs reflex vagal activity. OVX selectively decreased BRS(PE) but not BRS(SNP) and abolished the nicotine-induced impairment of either response. These effects of OVX were reversed after treatment with estrogen or the estrogen receptor modulator raloxifene. In atropine-treated rats, comparable BRS values were demonstrated in all rat preparations regardless of the estrogen or nicotine milieu. Collectively, the inhibition of vagal activity accounts for the depressant effect of chronic nicotine on baroreflex activity. Furthermore, contrary to nicotine's acute effects, the baroreflex-attenuating effect of chronic nicotine is exacerbated by estrogen. PMID:22619254

  18. Nicotine primes the effect of cocaine on the induction of LTP in the amygdala.

    PubMed

    Huang, Yan-You; Kandel, Denise B; Kandel, Eric R; Levine, Amir

    2013-11-01

    In human populations, there is a well-defined sequence of involvement in drugs of abuse, in which the use of nicotine or alcohol precedes the use of marijuana, which in turn, precedes the use of cocaine. The term "Gateway Hypothesis" describes this developmental sequence of drug involvement. In prior work, we have developed a mouse model to study the underlying metaplastic behavioral, cellular and molecular mechanisms by which exposure to one drug, namely nicotine, affects the response to another drug, namely cocaine. We found that nicotine enhances significantly the changes in synaptic plasticity in the striatum induced by cocaine (Levine et al., 2011). Here we ask: does the metaplastic effect of nicotine on cocaine also apply in the amygdala, a brain region that is involved in the orchestration of emotions and in drug addiction? We find that pretreatment with nicotine enhances long-term synaptic potentiation (LTP) in response to cocaine in the amygdala. Both short-term (1 day) and long-term (7 days) pre-exposure to nicotine facilitate the induction of LTP by cocaine. The effect of nicotine on LTP is unidirectional; exposure to nicotine following treatment with cocaine is ineffective. This metaplastic effect of nicotine on cocaine is long lasting but reversible. The facilitation of LTP can be obtained for 24 but not 40 days after cessation of nicotine. As is the case in the striatum, pretreatment with Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, simulates the priming effect of nicotine. These results provide further evidence that the priming effect of nicotine may be achieved, at least partially, by the inhibition of histone acetylation and indicate that the amygdala appears to be an important brain structure for the processing of the metaplastic effect of nicotine on cocaine. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. PMID:23597510

  19. Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

    SciTech Connect

    Biegon, A.; Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

    2010-01-12

    Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

  20. Insulin signaling genes modulate nicotine-induced behavioral responses in Caenorhabditis elegans.

    PubMed

    Wescott, Seth A; Ronan, Elizabeth A; Xu, X Z Shawn

    2016-02-01

    Insulin signaling has been suggested to modulate nicotine dependence, but the underlying genetic evidence has been lacking. Here, we used the nematode, Caenorhabditis elegans, to investigate whether genetic alterations in the insulin signaling pathway affect behavioral responses to nicotine. For this, we challenged drug-naive C. elegans with an acute dose of nicotine (100 μmol/l) while recording changes in their locomotion speed. Although nicotine treatment stimulated locomotion speed in wild-type C. elegans, the same treatment reduced locomotion speed in mutants defective in insulin signaling. This phenotype could be suppressed by mutations in daf-16, a gene encoding a FOXO transcription factor that acts downstream of insulin signaling. Our data suggest that insulin signaling genes, daf-2, age-1, pdk-1, akt-1, and akt-2, modulate behavioral responses to nicotine in C. elegans, indicating a genetic link between nicotine behavior and insulin signaling. PMID:26317299

  1. Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene

    PubMed Central

    Hartz, Sarah M.; Lin, Peng; Edenberg, Howard J.; Xuei, Xiaoling; Rochberg, Nanette; Saccone, Scott; Berrettini, Wade; Nelson, Elliot; Nurnberger, John; Bierut, Laura J.; Rice, John P.

    2011-01-01

    Objective Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. Method Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. Results To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2–2.4, P = 0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. Conclusion Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder. Psychiatr Genet 00:000–000. PMID:21191315

  2. Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

    PubMed

    Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

    2016-01-01

    Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use. PMID:26555360

  3. Bromoenol Lactone Attenuates Nicotine-Induced Breast Cancer Cell Proliferation and Migration

    PubMed Central

    Calderon, Lindsay E.; Liu, Shu; Arnold, Nova; Breakall, Bethany; Rollins, Joseph; Ndinguri, Margaret

    2015-01-01

    Objectives Calcium independent group VIA phospholipase A2 (iPLA2β) and Matrix Metalloproteinase-9 (MMP-9) are upregulated in many disease states; their involvement with cancer cell migration has been a recent subject for study. Further, the molecular mechanisms mediating nicotine-induced breast cancer cell progression have not been fully investigated. This study aims to investigate whether iPLA2β mediates nicotine-induced breast cancer cell proliferation and migration through both in-vitro and in-vivo techniques. Subsequently, the ability of Bromoenol Lactone (BEL) to attenuate the severity of nicotine-induced breast cancer was examined. Method and Results We found that BEL significantly attenuated both basal and nicotine-induced 4T1 breast cancer cell proliferation, via an MTT proliferation assay. Breast cancer cell migration was examined by both a scratch and transwell assay, in which, BEL was found to significantly decrease both basal and nicotine-induced migration. Additionally, nicotine-induced MMP-9 expression was found to be mediated in an iPLA2β dependent manner. These results suggest that iPLA2β plays a critical role in mediating both basal and nicotine-induced breast cancer cell proliferation and migration in-vitro. In an in-vivo mouse breast cancer model, BEL treatment was found to significantly reduce both basal (p<0.05) and nicotine-induced tumor growth (p<0.01). Immunohistochemical analysis showed BEL decreased nicotine-induced MMP-9, HIF-1alpha, and CD31 tumor tissue expression. Subsequently, BEL was observed to reduce nicotine-induced lung metastasis. Conclusion The present study indicates that nicotine-induced migration is mediated by MMP-9 production in an iPLA2β dependent manner. Our data suggests that BEL is a possible chemotherapeutic agent as it was found to reduce both nicotine-induced breast cancer tumor growth and lung metastasis. PMID:26588686

  4. Functional expression of human α9* nicotinic acetylcholine receptors in X. laevis oocytes is dependent on the α9 subunit 5' UTR.

    PubMed

    Filchakova, Olena; McIntosh, J Michael

    2013-01-01

    Nicotinic acetylcholine receptors (nAChRs) containing the α9 subunit are expressed in a wide variety of non-neuronal tissues ranging from immune cells to breast carcinomas. The α9 subunit is able to assemble into a functional homomeric nAChR and also co-assemble with the α10 subunit into functional heteromeric nAChRs. Despite the increasing awareness of the important roles of this subunit in vertebrates, the study of human α9-containing nAChRs has been severely limited by difficulties in its expression in heterologous systems. In Xenopus laevis oocytes, functional expression of human α9α10 nAChRs is very low compared to that of rat α9α10 nAChRs. When oocytes were co-injected with cRNA of α9 and α10 subunits of human versus those of rat, oocytes with the rat α9 human α10 combination had an ∼-fold higher level of acetylcholine-gated currents (I(ACh)) than those with the human α9 rat α10 combination, suggesting difficulties with human α9 expression. When the ratio of injected human α9 cRNA to human α10 cRNA was increased from 1∶1 to 5∶1, I(ACh) increased 36-fold (from 142±23 nA to 5171±748 nA). Functional expression of human α9-containing receptors in oocytes was markedly improved by appending the 5'-untranslated region of alfalfa mosaic virus RNA4 to the 5'-leader sequence of the α9 subunit cRNA. This increased the functional expression of homomeric human α9 receptors by 70-fold (from 7±1 nA to 475±158 nA) and of human α9α10 heteromeric receptors by 80-fold (from 113±62 nA to 9192±1137 nA). These findings indicate the importance of the composition of the 5' untranslated leader sequence for expression of α9-containing nAChRs. PMID:23717646

  5. Outcome of heroin-dependent adolescents presenting for opiate substitution treatment.

    PubMed

    Smyth, Bobby P; Fagan, John; Kernan, Kathy

    2012-01-01

    Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame. PMID:21940134

  6. Nicotine intake by snuff users.

    PubMed Central

    Russell, M A; Jarvis, M J; Devitt, G; Feyerabend, C

    1981-01-01

    Blood nicotine and cotinine concentrations were measured in 27 volunteers before and after taking snuff. Within 10 minutes after snuffing blood nicotine concentrations were comparable to those obtained after the 10 minutes or so that it takes to smoke a cigarette. Nicotine intake from snuffing was related to the experience of the snuffer. In daily and occasional snuffers increases in plasma nicotine concentrations averaged 77.7 and 12.3 nmol/l (12.6 and 2.0 ng/ml) respectively, while the novices showed no appreciable increase. The increase shown by thea daily snuffers was comparable to the average increase of 62.3 nmol/l (10.1 ng/ml) obtained from a single cigarette by a group of heavy smokers. The peak nicotine concentrations in the daily snuffers were also similar to the peak values in 136 heavy smokers--222.6 and 226-3 nmol/l (36.1 and 36.7 ng/ml), respectively. Unusual multiple-dose snuffing produced massive increases in plasma nicotine to concentrations that have never been recorded in smokers. The similarity of the concentrations produced by regular daily snuffing and regular daily smoking suggests that the plasma nicotine concentration has some controlling influence over the self-regulation of these two quite different forms of tobacco use. The rapid absorption of nicotine from snuff confirms its potential as an acceptable and relatively harmless substitute for smoking. PMID:6794710

  7. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats

    PubMed Central

    Palmatier, Matthew I.; Kellicut, Marissa R.; Sheppard, A. Brianna; Brown, Russell W.; Robinson, Donita L.

    2015-01-01

    Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects – the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4 mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30 s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign

  8. Drinking Trajectories From Adolescence to the Fifties Among Alcohol-Dependent Men*

    PubMed Central

    Jacob, Theodore; Koenig, Laura B.; Howell, Donelle N.; Wood, Phillip K.; Haber, Jon Randolph

    2009-01-01

    Objective: Although it has been recognized that the course of alcoholism may differ across individuals, little work has characterized drinking trajectories from drinking onset to midlife. Method: The current study examined trajectories of alcohol dependence from adolescence to the mid-50s in a sample of 420 men with a lifetime diagnosis of alcohol dependence. Men from the Vietnam Era Twin Registry were given the Lifetime Drinking History, which assesses the patterns of alcohol consumption and diagnostic symptoms for self-defined drinking phases. Phase data were converted into person-year data, with alcohol-dependence diagnosis coded as present or absent for each of 13 age groupings, starting with up to age 20 and ending with ages 54-56. Results: Latent growth mixture modeling was used to define four drinking trajectories: young-adult, late-onset, severe-nonchronic, and severe-chronic alcoholics. Further analyses with other diagnostic variables, other drinking variables, alcohol expectancies, personality scales, and religiousness scores were completed to differentiate men best categorized by each trajectory. Conclusions: Extension of Latent Growth Mixture Modeling (LGMM) into the mid-50s revealed that, although some individuals remain chronic alcohol users, others decline in alcohol problem use. Differences seen among these groups may help in the treatment of alcohol dependence, such that more energy can be spent treating those likely to be in the more severe trajectories. PMID:19895762

  9. Nicotinic Regulation of Energy Homeostasis

    PubMed Central

    2012-01-01

    Introduction: The ability of nicotine, the primary psychoactive substance in tobacco smoke, to regulate appetite and body weight is one of the factors cited by smokers that prevents them from quitting and is the primary reason for smoking initiation in teenage girls. The regulation of feeding and metabolism by nicotine is complex, and recent studies have begun to identify nicotinic acetylcholine receptor (nAChR) subtypes and circuits or cell types involved in this regulation. Discussion: We will briefly describe the primary anatomical and functional features of the input, output, and central integration structures of the neuroendocrine systems that regulate energy homeostasis. Then, we will describe the nAChR subtypes expressed in these structures in mammals to identify the possible molecular targets for nicotine. Finally, we will review the effects of nicotine and its withdrawal on feeding and energy metabolism and attribute them to potential central and peripheral cellular targets. PMID:22990212

  10. Personality Characteristics of Adolescents with Hallucinogen, Methamphetamine, and Cannabis Dependence: A Comparative Study

    ERIC Educational Resources Information Center

    Palmer, Glen A.; Daiss, Doyle D.

    2005-01-01

    A comparison of personality factors on scales of the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) was conducted with a sample of adolescents referred to a residential substance abuse treatment program. A total of sixty adolescents identified with hallucinogen (n = 20), cannabis (n = 20), or methamphetamine (n = 20) as their drug…

  11. PRENATAL NICOTINE EXPOSURE SELECTIVELY AFFECTS NICOTINIC RECEPTOR EXPRESSION IN PRIMARY AND ASSOCIATIVE VISUAL CORTICES OF THE FETAL BABOON

    PubMed Central

    Duncan, Jhodie R.; Garland, Marianne; Stark, Raymond I.; Myers, Michael M.; Fifer, William P.; Mokler, David J.; Kinney, Hannah C.

    2014-01-01

    Exposure to nicotine during pregnancy via maternal cigarette smoking is associated with visual deficits in children. This is possibly due to activation of nicotinic acetylcholine receptors (nAChRs) in the occipital cortex which are important in the development of visual mapping. Using a baboon model we explored the effects of prenatal nicotine on parameters in the primary and associated visual cortices. Pregnant baboons were infused with nicotine (0.5 mg/hr, i.v.) or saline from 86 days gestation. At 161 days gestation fetal brains were collected (n=5/group) and the occipital lobe assessed for nAChRs and markers of the serotonergic and catecholaminergic systems using tissue autoradiography and/or high performance liquid chromatography. Neuronal nAChRs and serotonergic markers were expressed in a region and subunit dependent manner. Prenatal nicotine exposure was associated with increased binding for 3H-epibatidine sensitive nAChRs in the primary visual cortex (BA 17) and BA 18, but not BA 19, of the associative visual cortex (p<0.05). Markers of the serotonergic or catecholaminergic systems were not significantly altered. Thus, prenatal nicotine exposure is associated with alterations in the cholinergic system in the occipital lobe which may aid in the explanation of the appearance of visual deficits in children from mothers who smoke during pregnancy. PMID:24903536

  12. Roles of nicotinic acetylcholine receptor β subunits in function of human α4-containing nicotinic receptors

    PubMed Central

    Wu, Jie; Liu, Qiang; Yu, Kewei; Hu, Jun; Kuo, Yen-Ping; Segerberg, Marsha; St John, Paul A; Lukas, Ronald J

    2006-01-01

    Naturally expressed nicotinic acetylcholine receptors (nAChR) containing α4 subunits (α4*-nAChR) in combination with β2 subunits (α4β2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. β4 subunits are also richly expressed and colocalize with α4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, α4β4-nAChR also may exist and play important functional roles. In this study, properties were determined of human α4β2- and α4β4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human α4β4-nAChR have ∼4-fold higher amplitude than those mediated via human α4β2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at α4β4-nAChR than at α4β2-nAChR. Cytisine and lobeline serve as full agonists at α4β4-nAChR but are only partial agonists at α4β2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional α4β2- and α4β4-nAChR. Whole-cell current responses show stronger inward rectification for α4β2-nAChR than for α4β4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR β2 or β4 subunits can combine with α4 subunits to generate two forms of α4*-nAChR with distinctive physiological and pharmacological features. Diversity in α4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence. PMID:16825297

  13. Possible role of afferent autonomic signals in abdominal organs in anorexic and cardiovascular responses to nicotine injection in rats.

    PubMed

    Yagi, Shintaro; Tanida, Mamoru; Satomi, Jun

    2015-05-27

    Smoking generally causes an increase in nicotine levels in the blood, affecting the brain components, such as the hypothalamus (feeding-related area) or the brain stem (cardiovascular control area). In terms of nicotine transmission to the brain, a new insight that the afferent vagal nerve in the liver is important for sensing increased nicotine levels in the blood and informing the brain was reported in an experiment with rats. However, it has not been clarified whether the afferent autonomic nerve system is implicated in feeding and cardiovascular responses to nicotine. Here, we examined the possible role of afferent autonomic nerve transmission in rats in regulating feeding behavior and cardiovascular functions by nicotine. An intravenous injection of nicotine dose dependently increased the blood pressure (BP) in urethane-anesthetized rats; high nicotine doses also led to an increase in BP in conscious rats. Further, an intravenous injection of nicotine for 3 days reduced food intake and body weight gain in rats. The weight-reducing action of intravenous nicotine was abolished by blocking the afferent sympathetic signals in the abdominal organs, but not the vagal nerve signals. Moreover, the hypertensive action of nicotine was not abolished either by afferent sympathectomy or by vagotomy. Thus, these data suggest that nicotine injected into the vein acts on the afferent sympathetic nerve in the abdominal organs and transmits signals to the brain for reducing body weight, but not for suppressing appetite or increasing BP. PMID:25875474

  14. [Nicotinic acid and nicotinamide].

    PubMed

    Kobayashi, M; Shimizu, S

    1999-10-01

    Nicotinic acid and nicotinamide are called niacin. They are the antipellagra vitamin essential to many animals for growth and health. In human being, niacin is believed necessary together with other vitamins for the prevention and cure of pellagra. Niacin is widely distributed in nature; appreciable amounts are found in liver, fish, yeast and cereal grains. Nicotinamide is a precursor of the coenzyme NAD and NADP. Some of the most understood metabolic processes that involve niacin are glycolysis, fatty acid synthesis and respiration. Niacin is also related to the following diseases: Hartnup disease; blue diaper syndrome; tryptophanuria; hydroxykynureninuria; xanthurenic aciduria; Huntington's disease. PMID:10540864

  15. Functional expression of human α7 nicotinic acetylcholine receptor in human embryonic kidney 293 cells.

    PubMed

    Gong, Yuan; Jiang, Ji-Hong; Li, Shi-Tong

    2016-09-01

    The functional expression of recombinant α7 nicotinic acetylcholine receptors in human embryonic kidney (HEK) 293 cells has presented a challenge. Resistance to inhibitors of cholinesterase 3 (RIC‑3) has been confirmed to act as a molecular chaperone of nicotinic acetylcholine receptors. The primary objectives of the present study were to investigate whether the co‑expression of human (h)RIC‑3 with human α7 nicotinic acetylcholine receptor in HEK 293 cells facilitates functional expression of the α7 nicotinic acetylcholine receptor. Subsequent to transfection, western blotting and polymerase chain reaction were used to test the expression of α7 nicotinic acetylcholine receptor and RIC-3. The α7 nicotinic acetylcholine receptor was expressed alone or co‑expressed with hRIC‑3 in the HEK 293 cells. Drug‑containing solution was then applied to the cells via a gravity‑driven perfusion system. Calcium influx in the cells was analyzed using calcium imaging. Nicotine did not induce calcium influx in the HEK 293 cells expressing human α7 nicotinic acetylcholine receptor only. However, in the cells co‑expressing human RIC‑3 and α7 nicotinic acetylcholine receptor, nicotine induced calcium influx via the α7 nicotinic acetylcholine receptor in a concentration‑dependent manner (concentration required to elicit 50% of the maximal effect=29.21 µM). Taken together, the results of the present study suggested that the co‑expression of RIC‑3 in HEK 293 cells facilitated the functional expression of the α7 nicotinic acetylcholine receptor. PMID:27430244

  16. Perinatal nicotine exposure suppresses PPARγ epigenetically in lung alveolar interstitial fibroblasts.

    PubMed

    Gong, M; Liu, J; Sakurai, R; Corre, A; Anthony, S; Rehan, V K

    2015-04-01

    Due to the active inhibition of the adipogenic programming, the default destiny of the developing lung mesenchyme is to acquire a myogenic phenotype. We have previously shown that perinatal nicotine exposure, by down-regulating PPARγ expression, accentuates this property, culminating in myogenic pulmonary phenotype, though the underlying mechanisms remained incompletely understood. We hypothesized that nicotine-induced PPARγ down-regulation is mediated by PPARγ promoter methylation, controlled by DNA methyltransferase 1 (DNMT1) and methyl CpG binding protein 2 (MeCP2), two known key regulators of DNA methylation. Using cultured alveolar interstitial fibroblasts and an in vivo perinatal nicotine exposure rat model, we found that PPARγ promoter methylation is strongly correlated with inhibition of PPARγ expression in the presence of nicotine. Methylation inhibitor 5-aza-2'-deoxycytidine restored the nicotine-induced down-regulation of PPARγ expression and the activation of its downstream myogenic marker fibronectin. With nicotine exposure, a specific region of PPARγ promoter was significantly enriched with antibodies against chromatin repressive markers H3K9me3 and H3K27me3, dose-dependently. Similar data were observed with antibodies against DNA methylation regulatory factors DNMT1 and MeCP2. The knock down of DNMT1 and MeCP2 abolished nicotine-mediated increases in DNMT1 and MeCP2 protein levels, and PPARγ promoter methylation, restoring nicotine-induced down regulation of PPARγ and upregulation of the myogenic protein, fibronectin. The nicotine-induced alterations in DNA methylation modulators DNMT1 and MeCP2, PPARγ promoter methylation, and its down-stream targets, were also validated in perinatally nicotine exposed rat lung tissue. These data provide novel mechanistic insights into nicotine-induced epigenetic silencing of PPARγ that could be exploited to design novel targeted molecular interventions against the smoke exposed lung injury in general and

  17. RIC-3 differentially modulates α4β2 and α7 nicotinic receptor assembly, expression, and nicotine-induced receptor upregulation

    PubMed Central

    2013-01-01

    Background Recent work has shown that the chaperone resistant to inhibitors of acetylcholinesterase (RIC-3) is critical for the folding, maturation and functional expression of a variety of neuronal nicotinic acetylcholine receptors. α7 nicotinic receptors can only assemble and functionally express in select lines of cells, provided that RIC-3 is present. In contrast, α4β2 nicotinic receptors can functionally express in many cell lines even without the presence of RIC-3. Depending on the cell line, RIC-3 has differential effects on α4β2 receptor function – enhancement in mammalian cells but inhibition in Xenopus oocytes. Other differences between the two receptor types include nicotine-induced upregulation. When expressed in cell lines, α4β2 receptors readily and robustly upregulate with chronic nicotine exposure. However, α7 nicotinic receptors appear more resistant and require higher concentrations of nicotine to induce upregulation. Could the coexpression of RIC-3 modulate the extent of nicotine-induced upregulation not only for α7 receptors but also α4β2 receptors? We compared and contrasted the effects of RIC-3 on assembly, trafficking, protein expression and nicotine-induced upregulation on both α7 and α4β2 receptors using fluorescent protein tagged nicotinic receptors and Förster resonance energy transfer (FRET) microscopy imaging. Results RIC-3 increases assembly and cell surface trafficking of α7 receptors but does not alter α7 protein expression in transfected HEK293T cells. In contrast, RIC-3 does not affect assembly of α4β2 receptors but increases α4 and β2 subunit protein expression. Acute nicotine (30 min exposure) was sufficient to upregulate FRET between α4 and β2 subunits. Surprisingly, when RIC-3 was coexpressed with α4β2 receptors nicotine-induced upregulation was prevented. α7 receptors did not upregulate with acute nicotine in the presence or absence of RIC-3. Conclusions These results provide interesting novel data

  18. Smoking cessation treatment for adolescents.

    PubMed

    Karpinski, Julie P; Timpe, Erin M; Lubsch, Lisa

    2010-10-01

    Cigarette smoking in the adolescent population remains a public health concern. A significant portion of the adolescent population currently uses tobacco. Nicotine is particularly addicting in adolescents, and quitting is difficult. The goals for adolescent cigarette smoking efforts must include both primary prevention and smoking cessation. Bupropion and nicotine replacement therapies-including nicotine patches, gum, and nasal spray-have been studied to a limited extent in the adolescent population. Varenicline has not been evaluated as a treatment modality in adolescents. Long-term quit rates in the pharmacotherapy trials have not been optimal; however, decreases in cigarettes smoked per day have been observed. Several evidencebased guidelines include recommendations for smoking cessation in adolescents that include counseling and pharmacotherapy. Pharmacotherapy may be instituted for some adolescents in addition to counseling and behavioral interventions. Therapy should be individualized, based on smoking patterns, patient preferences, and concomitant disease states. Smoking cessation support for parents should be instituted as well. The pharmacist can play a large role in helping the adolescent quit smoking. Further studies evaluating pharmacotherapy options for smoking cessation in adolescents are necessary. If pharmacotherapy is used, it should be individualized and combined with psychosocial and behavioral interventions. PMID:22477813

  19. Substance Use and Dependency Disorders in Adolescent Girls in Group Living Programs: Prevalence and Associations with Milieu Factors

    ERIC Educational Resources Information Center

    Baker, Amy J. L.; Ashare, Caryn; Charvat, Benjamin J.

    2009-01-01

    Fifty-three adolescent girls residing in community-based group-living child welfare programs were administered a standardized measure (SASS-2) in order to assess probability of a substance use/dependency disorder in this highly vulnerable population. Findings revealed that one third of the sample, and one half of the nonpregnant/parenting girls,…

  20. The Effects of Physical Training on Blood Lipid Profiles in Adolescents with Insulin-Dependent Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Campaigne, B. N.; And Others

    1985-01-01

    Fourteen adolescents with insulin-dependent diabetes mellitus (IDDM) participated in a 12-week exercise program to determine whether such training would bring about changes in blood lipid and lipoprotein profiles. The findings support the beneficial effects of regular exercise for individuals with IDDM. (MT)

  1. Developmental pathways to adolescent cannabis abuse and dependence: child maltreatment, emerging personality, and internalizing versus externalizing psychopathology.

    PubMed

    Oshri, Assaf; Rogosch, Fred A; Burnette, Mandi L; Cicchetti, Dante

    2011-12-01

    Child maltreatment is strongly associated with adolescent psychopathology and substance abuse and dependence. However, developmental processes unfolding from childhood into adolescence that delineate this trajectory are not well understood. The current study used path analysis in a structural equation modeling framework to examine multiple mediator models, including ego control, ego resiliency, and internalizing and externalizing symptoms to investigate this developmental process. Participants were 415 children, assessed across 3 waves of data, (i.e., at ages 7 to 9, 10 to 12, and 13 to 15). The sample included maltreated (n = 259) and nonmaltreated (n = 156) children; groups were comparable in sociodemographic characteristics. Findings support an transactional-ecological model by revealing a developmental sequence in which severity of early childhood maltreatment potentiates less adaptive childhood personality functioning, followed by externalizing problems in preadolescence, and ultimately adolescent cannabis abuse and dependence symptoms. A developmental pathway from child maltreatment to adolescent cannabis abuse and dependence symptoms via personality and preadolescent internalizing problems was not supported. Understanding developmental pathways by which maltreatment experiences increase risk for substance abuse and dependence symptoms in youth has far-reaching implications for the treatment and prevention of substance use disorders. PMID:21534646

  2. Mixed nicotinic and muscarinic features of cholinergic receptor coupled to secretion in bovine chromaffin cells.

    PubMed Central

    Shirvan, M H; Pollard, H B; Heldman, E

    1991-01-01

    Acetylcholine evokes release from cultured bovine chromaffin cells by a mechanism that is believed to be classically nicotinic. However, we found that the full muscarinic agonist oxotremorine-M (Oxo-M) induced a robust catecholamine (CA) secretion. By contrast, muscarine, pilocarpine, bethanechol, and McN-A-343 did not elicit any secretory response. Desensitization of the response to nicotine by Oxo-M and desensitization of the response to Oxo-M by nicotine suggest that both nicotine and Oxo-M were acting at the same receptor. Additional experiments supporting this conclusion show that nicotine-induced secretion and Oxo-M-induced secretion were similarly blocked by various muscarinic and nicotinic antagonists. Moreover, secretion induced by nicotine and Oxo-M were Ca2+ dependent, and both agonists induced 45Ca2+ uptake. Equilibrium binding studies showed that [3H]Oxo-M bound to chromaffin cell membranes with a Kd value of 3.08 x 10(-8) M and a Hill coefficient of 1.00, suggesting one binding site for this ligand. Nicotine inhibited Oxo-M binding in a noncompetitive manner, suggesting that both ligands bind at two different sites on the same receptor. We propose that the receptor on bovine chromaffin cells that is coupled to secretion represents an unusual cholinergic receptor that has both nicotinic and muscarinic features. Images PMID:2052567

  3. Nicotine quantity and packaging disclosure in smoked and smokeless tobacco products in India

    PubMed Central

    Sharma, Priyamvada; Murthy, Pratima; Shivhare, Parul

    2015-01-01

    Objectives: A variety of smoked and smokeless tobacco products with varying nicotine content are accessible in India. Nicotine quantity in tobacco products has direct bearing on tobacco dependence. Our objective was to estimate nicotine content in various types of smoked and smokeless products. Disclosure for essential health warning was also checked. Materials and Methods: Liquid-liquid extraction was used for nicotine extraction and high-performance thin layer chromatography technique was applied for quantification of nicotine in seventy-one smoked and smokeless tobacco products. Results: Significant variation in nicotine content was observed across products. In smoked tobacco, nicotine content varied from 1.01 to 13.0 mg/rod, while in smokeless tobacco products it ranged from 0.8 mg/g to 50.0 mg/g. Moisture content varied from 9% to 21%. Conclusion: This work lists a range of smoked and smokeless tobacco products available in this region. We report a wide variability in nicotine quantity across smoked and smokeless tobacco products. Such variation in nicotine content may have important implications for tobacco cessation interventions and policies PMID:26288479

  4. Mixed nicotinic and muscarinic features of cholinergic receptor coupled to secretion in bovine chromaffin cells

    SciTech Connect

    Shirvan, M.H.; Pollard, H.B.; Heldman, E. )

    1991-06-01

    Acetylcholine evokes release from cultured bovine chromaffin cells by a mechanism that is believed to be classically nicotinic. However, the authors found that the full muscarinic agonist oxotremorine-M (Oxo-M) induced a robust catecholamine (CA) secretion. By contrast, muscarine, pilocarpine, bethanechol, and McN-A-343 did not elicit any secretory response. Desensitization of the response to nicotine by Oxo-M and desensitization of the response to Oxo-M by nicotine suggest that both nicotine and Oxo-M were acting at the same receptor. Additional experiments supporting this conclusion show that nicotine-induced secretion and Oxo-M-induced secretion were similarly blocked by various muscarinic and nicotinic antagonists. Moreover, secretion induced by nicotine and Oxo-M were Ca{sup 2+} dependent, and both agonists induced {sup 45}Ca{sup 2+} uptake. Equilibrium binding studies showed that ({sup 3}H)Oxo-M bound to chromaffin cell membranes with a K{sub d} value of 3.08 {times} 10{sup {minus}8}M and a Hill coefficient of 1.00, suggesting one binding site for this ligand. Nicotine inhibited Oxo-M binding in a noncompetitive manner, suggesting that both ligands bind at two different sites on the same receptor. They propose that the receptor on bovine chromaffin cells that is coupled to secretion represents an unusual cholinergic receptor that has both nicotinic and muscarinic features.

  5. Nicotine promotes cell proliferation via {alpha}7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

    SciTech Connect

    Wong, Helen Pui Shan; Yu Le; Lam, Emily Kai Yee; Tai, Emily Kin Ki; Wu, William Ka Kei; Cho, Chi Hin . E-mail: chcho@cuhk.edu.hk

    2007-06-15

    Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a {beta}{sub 1}- and {beta}{sub 2}-selective antagonist, respectively, suggesting the role of {beta}-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-{beta}-hydroxylase (D{beta}H) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferation and adrenaline production. Expression of {alpha}7-nicotinic acetylcholine receptor ({alpha}7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an {alpha}7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and D{beta}H expression as well as adrenaline production. Taken together, through the action on {alpha}7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and {beta}-adrenergic activation. These data reveal the contributory role {alpha}7-nAChR and {beta}-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer.

  6. Nicotine response genetics in the zebrafish

    PubMed Central

    Petzold, Andrew M.; Balciunas, Darius; Sivasubbu, Sridhar; Clark, Karl J.; Bedell, Victoria M.; Westcot, Stephanie E.; Myers, Shelly R.; Moulder, Gary L.; Thomas, Mark J.; Ekker, Stephen C.

    2009-01-01

    Tobacco use is predicted to result in over 1 billion deaths worldwide by the end of the 21st century. How genetic variation contributes to the observed differential predisposition in the human population to drug dependence is unknown. The zebrafish (Danio rerio) is an emerging vertebrate model system for understanding the genetics of behavior. We developed a nicotine behavioral assay in zebrafish and applied it in a forward genetic screen using gene-breaking transposon mutagenesis. We used this method to molecularly characterize bdav/cct8 and hbog/gabbr1.2 as mutations with altered nicotine response. Each have a single human ortholog, identifying two points for potential scientific, diagnostic, and drug development for nicotine biology and cessation therapeutics. We show this insertional method generates mutant alleles that are reversible through Cre-mediated recombination, representing a conditional mutation system for the zebrafish. The combination of this reporter-tagged insertional mutagen approach and zebrafish provides a powerful platform for a rich array of questions amenable to genetic-based scientific inquiry, including the basis of behavior, epigenetics, plasticity, stress, memory, and learning. PMID:19858493

  7. Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking

    PubMed Central

    2013-01-01

    Introduction: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. Methods: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Results: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2±15.7ng/ml (mean ± SD) within 1–4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. Conclusions: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics. PMID:23239844

  8. Craving and nicotine withdrawal in a Spanish smoking cessation sample.

    PubMed

    Piñeiro, Bárbara; López-Durán, Ana; Fernández del Río, Elena; Martínez, Úrsula; Brandon, Thomas H; Becoña, Elisardo

    2014-01-01

    Craving and nicotine withdrawal syndrome (NWS) are components of the tobacco use disorder in DSM-5. They both appear after smoking cessation or an abrupt reduction in tobacco use, and they are associated with both short and long-term smoking-cessation outcomes. The aim of the present study was to examine the association of craving and withdrawal with smoking cessation at the end of the treatment and relapse at 3 months follow-up in a Spanish sample of smokers. The sample comprised 342 smokers (37.7% men; 62.3% women) receiving a cognitive-behavioral treatment for smoking cessation. The assessments of craving and withdrawal were conducted using the Minnesota Nicotine Withdrawal Scale. Abstainers at the end of the treatment, compared to non abstainers, showed significantly lower post-treatment withdrawal, and post-treatment craving. Furthermore, they had lower scores in pre-treatment nicotine dependence. Among abstainers, craving decreased significantly from pre-cessation levels, while in those participants who did not quit smoking it remained on the same levels. High nicotine dependence was a predictor of smoking at the end of the treatment, whereas high nicotine withdrawal predicted relapse at 3 months. Findings support the robust role of craving and NWS in smoking cessation and relapse, although they differ in their specific patterns of change over time. PMID:25314038

  9. Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use

    PubMed Central

    Melroy-Greif, W. E.; Stitzel, J. A.; Ehringer, M. A.

    2016-01-01

    Nicotinic acetylcholine receptors are ligand-gated ion channels that exogenously bind nicotine. Nicotine produces rewarding effects by interacting with these receptors in the brain’s reward system. Unlike other receptors, chronic stimulation by an agonist induces an upregulation of receptor number that is not due to increased gene expression in adults; while upregulation also occurs during development and adolescence there have been some opposing findings regarding a change in corresponding gene expression. These receptors have also been well studied with regard to human genetic associations and, based on evidence suggesting shared genetic liabilities between substance use disorders, numerous studies have pointed to a role for this system in comorbid drug use. This review will focus on upregulation of these receptors in adulthood, adolescence and development, as well as the findings from human genetic association studies which point to different roles for these receptors in risk for initiation and continuation of drug use. PMID:26351737

  10. Whisker experience-dependent mGluR signaling maintains synaptic strength in the mouse adolescent cortex.

    PubMed

    Kubota, Jun; Mikami, Yoshinori; Kanemaru, Kazunori; Sekiya, Hiroshi; Okubo, Yohei; Iino, Masamitsu

    2016-08-01

    Sensory experience-dependent plasticity in the somatosensory cortex is a fundamental mechanism of adaptation to the changing environment not only early in the development but also in adolescence and adulthood. Although the mechanisms underlying experience-dependent plasticity during early development have been well documented, the corresponding understanding in the mature cortex is less complete. Here, we investigated the mechanism underlying whisker deprivation-induced synaptic plasticity in the barrel cortex in adolescent mice. Layer 4 (L4) to L2/3 excitatory synapses play a crucial role for whisker experience-dependent plasticity in rodent barrel cortex and whisker deprivation is known to depress synaptic strength at L4-L2/3 synapses in adolescent and adult animals. We found that whisker deprivation for 5 days or longer decreased the presynaptic glutamate release probability at L4-L2/3 synapses in the barrel cortex in adolescent mice. This whisker deprivation-induced depression was restored by daily administration of a positive allosteric modulator of the type 5 metabotropic glutamate receptor (mGluR5). On the other hand, the administration of mGluR5 antagonists reproduced the effect of whisker deprivation in whisker-intact mice. Furthermore, chronic and selective suppression of inositol 1,4,5-trisphosphate (IP3 ) signaling in postsynaptic L2/3 neurons decreased the presynaptic release probability at L4-L2/3 synapses. These findings represent a previously unidentified mechanism of cortical plasticity, namely that whisker experience-dependent mGluR5-IP3 signaling in the postsynaptic neurons maintains presynaptic function in the adolescent barrel cortex. PMID:27225340

  11. Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction.

    PubMed

    Benowitz, N L

    1991-05-01

    Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks. PMID:1859911

  12. Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking.

    PubMed

    Leão, Rodrigo M; Cruz, Fábio C; Vendruscolo, Leandro F; de Guglielmo, Giordano; Logrip, Marian L; Planeta, Cleopatra S; Hope, Bruce T; Koob, George F; George, Olivier

    2015-04-15

    Alcohol and nicotine are the two most co-abused drugs in the world. Previous studies have shown that nicotine can increase alcohol drinking in nondependent rats, yet it is unknown whether nicotine facilitates the transition to alcohol dependence. We tested the hypothesis that chronic nicotine will speed up the escalation of alcohol drinking in rats and that this effect will be accompanie