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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.

  2. Risk and Protective Factors for Nicotine Dependence in Adolescence

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  3. 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

  4. 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

  5. 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…

  6. 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…

  7. THE RELATIONSHIP BETWEEN IMPULSIVITY, -TAKING PROPENSITY AND NICOTINE DEPENDENCE AMONG OLDER ADOLESCENT SMOKERS

    PubMed Central

    Ryan, Katherine K.; MacKillop, James; Carpenter, Matthew J.

    2012-01-01

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

  8. Early Emerging Nicotine Dependence Symptoms in Adolescence Predict Daily Smoking in Young Adulthood

    PubMed Central

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

    2015-01-01

    Purpose The present study evaluated the predictive validity of individual early emerging nicotine dependence symptoms in adolescence on smoking behavior in young adulthood. Methods A total of 492 adolescents who, at baseline, had not smoked more than 100 cigarettes in their lifetime and 123 adolescents who smoked more than 100 cigarettes lifetime, and who participated in the 6-year follow-up assessment were included in the present analyses. Predictive validity of 10 nicotine dependence items administered at baseline was evaluated at the 6 year follow-up when the sample had entered young adulthood (mean age=21.6). Results Among adolescents who had smoked fewer than 100 cigarettes, experiencing higher levels of overall nicotine dependence as well as individual symptoms at baseline longitudinally predicted an increase in risk for daily smoking in young adulthood, after controlling for baseline smoking and other tobacco use. For adolescents who had smoked more than 100 cigarettes at baseline, level of nicotine dependence and individual symptom endorsement did not predict smoking behavior in young adulthood. Conclusions These findings add to accumulating evidence that early emerging dependence symptoms reported at low levels of smoking exposure signal a greater propensity for continued smoking behavior. Screening for these early emerging symptoms among novice adolescent smokers represents an important and unused tool in tobacco control efforts aimed at preventing the development of chronic smoking patterns. PMID:25840749

  9. Predictors of nicotine dependence symptoms among never-smoking adolescents: A longitudinal analysis from the Nicotine Dependence in Teens Study

    PubMed Central

    Racicot, Simon; McGrath, Jennifer J.; Karp, Igor; O’Loughlin, Jennifer

    2017-01-01

    Background Recent cross-sectional studies suggest some adolescents who have never smoked cigarettes experience nicotine dependence (ND) symptoms and that exposure to second-hand smoke, social exposure to smoking, and alcohol use are plausible correlates. The aim of this study was to replicate and extend these findings by investigating possible predictors of ND symptoms longitudinally. Method Participants included 847 secondary school students who had never smoked cigarettes enrolled in the Nicotine Dependence in Teens Study. Adolescents completed self-report questionnaires measuring smoking status, ND symptoms, and risk factors for ND in smokers (i.e., socio-demographic indicators, social exposure to smoking, psychosocial indicators, and substance use) in 20 survey cycles from 7 to 11th grade. Generalized estimating equations, which account for repeated measures within individuals, were used to test the predictors of ND symptoms. Results Consistent with previous research, 7.8% of never-smokers across all cycles endorsed at least one ND symptom. Younger age (p ≤ .001), country of birth (p ≤ .05), peer smoking (p ≤ .001), teacher smoking (p ≤ .05), depression (p ≤ .05), stress (p ≤ .001), lower self-esteem (p ≤ .05), impulsivity (p ≤ .05), and alcohol use (p ≤ .001) predicted greater ND symptoms in multivariable modeling. Conclusions Replicating previous cross-sectional findings, peer smoking and alcohol use predicted ND symptoms among never-smoking adolescents. Extending these findings, previous predictors only observed among ever-smokers, including socio-demographic and psychosocial indicators, also predicted ND symptoms. This longitudinal investigation demonstrated the temporal relation of the predictors preceding ND symptoms. Future research should consider longer prospective studies with younger children to capture early onset of ND symptoms and with longer follow-up to detect eventual smoking uptake. PMID:23195923

  10. 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.

  11. 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.

  12. 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

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

    2015-02-01

    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.

  13. 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.

  14. Progression of nicotine dependence, mood level, and mood variability in adolescent smokers.

    PubMed

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

    2016-06-01

    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. (PsycINFO Database Record

  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. Reciprocal Associations Between Cigarette Consumption and DSM-IV Nicotine Dependence Criteria in Adolescent Smokers

    PubMed Central

    Hu, Mei-Chen; Griesler, Pamela C.; Wall, Melanie M.; Kandel, Denise B.

    2014-01-01

    Aims To examine the interrelationships between cigarette consumption and DSM-IV nicotine dependence (ND) criteria from smoking onset in adolescence up to seven years later, adjusting for alcohol consumption and DSM-IV alcohol dependence (AD) criteria. Design A cohort drawn from grades 6-10 in an urban school system was interviewed five times at 6-month intervals (Waves 1-5) and 4.5 years later (Wave 6). A parent was interviewed three times. Setting Chicago, Illinois. Participants Recent smokers (n=409). Measurements Structured household interviews ascertained number of cigarettes smoked, DSM-IV ND symptoms, drinks consumed, DSM-IV AD symptoms, and selected covariates. Analysis Reciprocal prospective associations between number of cigarettes smoked and ND criteria, controlling for time-varying alcohol consumption and dependence criteria, were examined with cross-lagged models. Findings Reciprocal associations between number of cigarettes smoked and ND criteria were both significant. Cigarette consumption had stronger associations with later ND (β=0.25, 95% CI=0.17-0.32) than dependence had with later cigarette consumption (β=0.09, 95% CI=0.01-0.16). Alcohol and cigarette consumption influenced each other; AD scores were associated with later ND scores but not the reverse. Reports of pleasant initial experiences from smoking were positively associated with cigarette consumption and ND the first year after smoking onset; later smoking onset was negatively associated with cigarette consumption the seventh year after onset; parental ND predicted cigarette consumption and ND throughout. Conclusions In adolescent smokers, higher cigarette consumption predicts later severity of DSM-IV nicotine dependence more than the reverse. Smoking and drinking also influence each other mutually over time. PMID:24845775

  17. 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.

  18. Treatment of nicotine dependence.

    PubMed

    Haxby, D G

    1995-02-01

    Drug and nondrug interventions used in treating nicotine dependence are reviewed. Tobacco use is the leading preventable cause of death in the United States. Risks of smoking-related disease and death decline sharply when smokers quit, but 26% of Americans continue to smoke. Most smokers find it extremely difficult to quit smoking because of their nicotine addiction. Nonpharmacologic interventions used to promote smoking cessation include behavioral therapy, setting a specific date for quitting, receiving advice to quit from a health care professional, follow-up visits to review progress, self-help approaches, group counseling, filtration devices, hypnosis, and acupuncture. The efficacy of these approaches ranges from substantial to almost nil. The only pharmacologic agent with FDA-approved labeling for use in smoking-cessation therapy is nicotine. When used in conjunction with appropriate nonpharmacologic interventions, nicotine-replacement therapy roughly doubles the rate of quitting obtained with placebo. Nicotine-replacement therapies consist of nicotine transdermal (patch) systems and nicotine chewing gum. The nicotine patch is the first-line replacement therapy because it is effective when accompanied by only minimal (as opposed to more intensive) nonpharmacologic interventions and because it is easier to use and comply with than gum. Clonidine, antidepressants, and buspirone require further study to determine what role, if any, they should play in the treatment of nicotine dependence. The stages of smoking cessation are precontemplation, contemplation, action, and maintenance; interventions are selected on the basis of the stage the smoker is in. Nicotine dependence is difficult to treat, but there are aids that boost a smoker's chances of quitting. Nicotine patches and chewing gum offer the most effective pharmacologic options, especially when combined with behavioral interventions and counseling.

  19. 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

  20. Nicotine and the adolescent brain.

    PubMed

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

    2015-08-15

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

  1. 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.

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

    PubMed

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

    2011-12-01

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

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

    PubMed

    Kelley, Brian M; Rowan, James D

    2004-01-01

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

  4. Nicotine dependence and smoking cessation.

    PubMed

    Tan, Linxiang; Tang, Quansheng; Hao, Wei

    2009-11-01

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

  5. Prenatal nicotine exposure alters the responses to subsequent nicotine administration and withdrawal in adolescence: Serotonin receptors and cell signaling.

    PubMed

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

    2006-11-01

    Offspring of women who smoke during pregnancy are themselves more likely to take up smoking in adolescence, effects that are associated with a high rate of depression and increased sensitivity to withdrawal symptoms. To evaluate the biological basis for this relationship, we assessed effects on serotonin (5-hydroxytryptamine, 5HT) receptors and 5HT-mediated cellular responses in rats exposed to nicotine throughout prenatal development and then given nicotine in adolescence (postnatal days PN30-47.5), using regimens that reproduce plasma nicotine levels found in smokers. Evaluations were then made during the period of adolescent nicotine treatment and for up to one month after the end of treatment. Prenatal nicotine exposure, which elicits damage to 5HT projections in the cerebral cortex and striatum, produced sex-selective changes in the expression of 5HT(1A) and 5HT2 receptors, along with induction of adenylyl cyclase (AC), leading to sensitization of heterologous inputs operating through this signaling pathway. Superimposed on these effects, the AC response to 5HT was shifted toward inhibition. By itself, adolescent nicotine administration, which damages the same pathways, produced similar effects on receptors and the 5HT-mediated response, but a smaller overall induction of AC. Animals exposed to prenatal nicotine showed a reduced response to nicotine administered in adolescence, results in keeping with earlier findings of persistent desensitization. Our results indicate that prenatal nicotine exposure alters parameters of 5HT synaptic communication lasting into adolescence and changes the response to nicotine administration and withdrawal in adolescence, actions which may contribute to a subpopulation especially vulnerable to nicotine dependence.

  6. 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

  7. 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.

  8. Nicotine Dependence Measures for Perinatal Women.

    PubMed

    Yang, Irene; Hall, Lynne A

    2016-03-02

    This integrative review provides an overview of nicotine dependence measures used with perinatal women and an evaluation of their psychometric properties. Fifty-five articles that met inclusion and exclusion criteria were identified from five different databases. Most of the studies used the Fagerström Test for Nicotine Dependence (FTND). Other approaches included diagnostic tests, the Wisconsin Inventory of Smoking Dependence Motives (WISDM), the Tobacco Dependence Screener, and single-item measures. This review indicated that the FTND may not be the best option for measuring nicotine dependence in this population. The WISDM is a newer instrument that has excellent psychometric properties and captures nonnicotinic dimensions of nicotine dependence relevant to women. Future research is needed to assess its reliability in the perinatal population. Other recommendations from this review include the use of biomarker validation, thorough psychometric reporting on nicotine dependence instruments, and the use of multiple instruments to maximize comparability between nicotine dependence instruments.

  9. 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.

  10. Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

    PubMed Central

    O’Dell, Laura E.; Torres, Oscar V.; Natividad, Luis A.; Tejeda, Hugo A.

    2012-01-01

    Vulnerability to nicotine addiction is significantly increased in individuals who begin smoking during adolescence; however, the underlying mechanisms of this phenomenon remain unclear. This study examined the motivational effects of nicotine withdrawal in adolescent (PND 27–42) and adult (PND 60–75) rats using the conditioned place aversion paradigm. Male Wistar rats were tested for their initial preference for either of two distinct compartments of our conditioning apparatus. Rats were then implanted with subcutaneous (sc) pumps that produce equivalent blood plasma levels of nicotine for 14 days. Conditioning was conducted over the last 8 days of nicotine exposure. Rats received the nicotinic antagonist mecamylamine (1.5 or 3.0 mg/kg, sc) to precipitate withdrawal in their initially preferred compartment, and on alternate days they received saline in their non-preferred compartment. Following conditioning, rats were re-tested for their preference for each compartment. A subsequent study was conducted to examine potential developmental differences in learning place aversion produced by another aversive stimulus, lithium chloride (LiCl). Rats received LiCl (0, 10, 30, or 100 mg/kg, sc) in their initially preferred side using similar conditioning procedures. Adults displayed robust place aversion produced by nicotine withdrawal. This effect was lower in adolescent rats even in a group of young rats that received 7 additional days of nicotine exposure prior to conditioning. This developmental difference was specific to nicotine withdrawal since there were no differences between adolescents and adults in learning place aversion with LiCl. Our findings demonstrating reduced effects of nicotine withdrawal constitute a powerful basis for the increased vulnerability to nicotine dependence during adolescence. PMID:17184972

  11. Nicotine Increases Alcohol Intake in Adolescent Male Rats

    PubMed Central

    Lárraga, Armando; Belluzzi, James D.; Leslie, Frances M.

    2017-01-01

    self-administration in adolescent males also increased subsequent oral EtOH intake. These findings suggest that brain mechanisms underlying the reinforcing effects of EtOH and nicotine are both age- and sex-dependent, and that tobacco or e-cigarette use may increase the vulnerability of teenage boys to alcohol abuse. PMID:28275339

  12. Sex-dependent effects of nicotine on the developing brain.

    PubMed

    Cross, Sarah J; Linker, Kay E; Leslie, Frances M

    2017-01-02

    The use of tobacco products represents a major public health concern, especially among women. Epidemiological data have consistently demonstrated that women have less success quitting tobacco use and a higher risk for developing tobacco-related diseases. The deleterious effects of nicotine are not restricted to adulthood, as nicotinic acetylcholine receptors regulate critical aspects of neural development. However, the exact mechanisms underlying the particular sensitivity of women to develop tobacco dependence have not been well elucidated. In this mini-review, we show that gonadal hormone-mediated sexual differentiation of the brain may be an important determinant of sex differences in the effects of nicotine. We highlight direct interactions between sex steroid hormones and ligand-gated ion channels critical for brain maturation, and discuss the extended and profound sexual differentiation of the brain. We emphasize that nicotine exposure during the perinatal and adolescent periods interferes with normal sexual differentiation and can induce long-lasting, sex-dependent alterations in neuronal structure, cognitive and executive function, learning and memory, and reward processing. We stress important age and sex differences in nicotine's effects and emphasize the importance of including these factors in preclinical research that models tobacco dependence. © 2016 Wiley Periodicals, Inc.

  13. Nicotine exposure in adolescence alters the response of serotonin systems to nicotine administered subsequently in adulthood.

    PubMed

    Slotkin, Theodore A; Seidler, Frederic J

    2009-01-01

    Developmental nicotine exposure produces lasting changes in serotonin (5-HT) function. We gave nicotine to adolescent rats (postnatal days, PD, 30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in young adulthood (PD 90-107), focusing on 5-HT(1A) and 5-HT(2) receptors and the 5-HT transporter during nicotine treatment (PD 105) and withdrawal (PD 110, 120, 130), and long-term changes (PD 180). Adolescent nicotine exposure by itself evoked long-term elevations in cerebrocortical binding parameters in males that emerged in young adulthood. Nicotine given in adulthood produced transient elevations in 5-HT receptor expression in both males and females during withdrawal, and persistent upregulation in the male cerebral cortex. In contrast, females showed decrements in cerebrocortical 5-HT receptors by PD 180. Adolescent nicotine exposure altered the responses to nicotine given in adulthood, sensitizing the initial effects and changing both the withdrawal response and long-term actions. Our results thus provide mechanistic evidence that nicotine exposure, during the period in which nearly all smokers begin to use tobacco, reprograms the future response of 5-HT systems to nicotine.

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

    PubMed

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

    2014-03-01

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

  15. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

    PubMed Central

    Zuo, Lingjun; Garcia-Milian, Rolando; Guo, Xiaoyun; Zhong, Chunlong; Tan, Yunlong; Wang, Zhiren; Wang, Jijun; Wang, Xiaoping; Kang, Longli; Lu, Lu; Chen, Xiangning; Li, Chiang-Shan R.; Luo, Xingguang

    2016-01-01

    It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs) play important roles in nicotine dependence (ND) and influence the number of cigarettes smoked per day (CPD) in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs) and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4). These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4, CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD. PMID:27827986

  16. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence.

    PubMed

    Zuo, Lingjun; Garcia-Milian, Rolando; Guo, Xiaoyun; Zhong, Chunlong; Tan, Yunlong; Wang, Zhiren; Wang, Jijun; Wang, Xiaoping; Kang, Longli; Lu, Lu; Chen, Xiangning; Li, Chiang-Shan R; Luo, Xingguang

    2016-11-07

    It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs) play important roles in nicotine dependence (ND) and influence the number of cigarettes smoked per day (CPD) in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs) and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4). These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4,CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.

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

    PubMed

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

    2015-03-01

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

  18. Constitutional mechanisms of vulnerability and resilience to nicotine dependence.

    PubMed

    Hiroi, N; Scott, D

    2009-07-01

    The core nature of nicotine dependence is evident in wide variations in how individuals become and remain smokers. Individuals with pre-existing behavioral traits are more likely to develop nicotine dependence and experience difficulty when attempting to quit. Many molecular factors likely contribute to individual variations in the development of nicotine dependence and behavioral traits in complex manners. However, the identification of such molecules has been hampered by the phenotypic complexity of nicotine dependence and the complex ways molecules affect elements of nicotine dependence. We hypothesize that nicotine dependence is, in part, a result of interactions between nicotine and pre-existing behavioral traits. This perspective suggests that the identification of the molecular bases of such pre-existing behavioral traits will contribute to the development of effective methods for reducing smoking dependence and for helping smokers to quit.

  19. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    PubMed

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

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

  20. Female rats display dose-dependent differences to the rewarding and aversive effects of nicotine in an age-, hormone-, and sex-dependent manner

    PubMed Central

    Torres, Oscar V.; Natividad, Luis A.; Tejeda, Hugo A.; Van Weelden, Susan A.

    2009-01-01

    Introduction The objective of this study was to examine age-, hormone-, and sex-dependent differences to the behavioral effects of nicotine using place-conditioning procedures in female rats. Methods Animals received nicotine in their initially non-preferred side and saline on alternate days in their initially preferred side. Following four conditioning trials, rats were retested for their preference. To examine developmental differences, we compared the effects of various nicotine doses in female and male adolescent and adult rats. To examine whether our developmental differences are specific to nicotine, we included adolescent and adult females that were conditioned with various amphetamine doses. To examine the influence of hormones on the behavioral effects of nicotine, we compared the effects of various nicotine doses in intact females that were tested during different phases of the estrous cycle and in separate females that were ovariectomized. Result The rewarding effects of nicotine were observed at a lower nicotine dose in adolescents versus adults. Amphetamine produced similar rewarding effects across age groups in females. The shifts in preference produced by nicotine were similar across the different phases of estrous. Females lacking ovarian hormones did not display rewarding effects of nicotine at any dose. The rewarding effects of nicotine were enhanced in adult female versus male rats. An intermediate nicotine dose produced rewarding effects in adolescent male but not female rats, suggesting that developmental differences to nicotine may be enhanced in males. Conclusion In females, nicotine reward is enhanced during adolescence and is facilitated by the presence of ovarian hormones. PMID:19629450

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

    PubMed

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

    2015-09-15

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

  2. Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex

    PubMed Central

    Counotte, Danielle S.; Goriounova, Natalia A.; Moretti, Milena; Smoluch, Marek T.; Irth, Hubertus; Clementi, Francesco; Schoffelmeer, Anton N. M.; Mansvelder, Huibert D.; Smit, August B.; Gotti, Cecilia; Spijker, Sabine

    2013-01-01

    Adolescence is a critical developmental period during which most adult smokers initiate their habit. Adolescents are more vulnerable than adults to nicotine’s long-term effects on addictive and cognitive behavior. We investigated whether adolescent nicotine exposure in rats modifies expression of nicotinic acetylcholine receptors (nAChRs) in medial prefrontal cortex (mPFC) in the short and/or long term, and whether this has functional consequences. Using receptor binding studies followed by immunoprecipitation of nAChR subunits, we showed that adolescent nicotine exposure, as compared with saline, caused an increase in mPFC nAChRs containing α4 or β2 subunits (24 and 18%, respectively) 24 h after the last injection. Nicotine exposure in adulthood had no such effect. This increase was transient and was not observed 5 wk following either adolescent or adult nicotine exposure. In line with increased nAChRs expression 1 d after adolescent nicotine exposure, we observed a 34% increase in amplitude of nicotine-induced spontaneous inhibitory postsynaptic currents in layer II/III mPFC pyramidal neurons. These effects were transient and specific, and observed only acutely after adolescent nicotine exposure, but not after 5 wk, and no changes were observed in adult-exposed animals. The acute nicotine-induced increase in α4β2-containing receptors in adolescents interferes with the normal developmental decrease (37%) of these receptors from early adolescence (postnatal day 34) to adulthood (postnatal day 104) in the mPFC. Together, this suggests that these receptors play a role in mediating the acute rewarding effects of nicotine and may underlie the increased sensitivity of adolescents to nicotine. PMID:22308197

  3. Prosocial effects of nicotine and ethanol in adolescent rats through partially dissociable neurobehavioral mechanisms.

    PubMed

    Trezza, Viviana; Baarendse, Petra J J; Vanderschuren, Louk J M J

    2009-11-01

    The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at doses that reduced anxiety. The effects of nicotine on social play were blocked by the opioid receptor antagonist naloxone, the CB(1) cannabinoid receptor antagonist SR141716A, and the dopamine receptor antagonist alpha-flupenthixol. The effects of ethanol were blocked by SR141716A and alpha-flupenthixol, but not by naloxone. Combined administration of subeffective doses of nicotine and ethanol only modestly enhanced social play. These results show that the facilitatory effects of nicotine and ethanol on social play are behaviorally specific and mediated through neurotransmitter systems involved in positive emotions and motivation, through partially dissociable mechanisms. Furthermore, the stimulating effects of nicotine and ethanol on social play behavior are independent of their anxiolytic-like properties.

  4. Age-dependent effects of initial exposure to nicotine on serotonin neurons.

    PubMed

    Bang, S J; Commons, K G

    2011-04-14

    Adolescence is a critical vulnerable period during which exposure to nicotine greatly enhances the possibility to develop drug addiction. Growing evidence suggests that serotonergic (5-HT) neurotransmission may contribute to the initiation and maintenance of addictive behavior. As the dorsal raphe (DR) and median raphe (MnR) nuclei are the primary 5-HT source to the forebrain, the current study tested the hypothesis that there are age-dependent effects of acute nicotine administration on activation of 5-HT neurons within these regions. Both adolescent (Postnatal day 30) and adult (Postnatal day 70) male Sprague-Dawley rats received subcutaneous injection of either saline or nicotine (0.2, 0.4, or 0.8 mg/kg). Subsequently, the number of 5-HT cells that were double-labeled for Fos and tryptophan hydroxylase was counted in seven subregions within the DR and the entire MnR. The results show that acute nicotine injection induces Fos expression in 5-HT neurons in a region-specific manner. In addition, adolescents show broader regional activations at either a lower (0.2 mg/kg) and a higher (0.8 mg/kg) dose of nicotine, displaying a unique U-shape response curve across doses. In contrast, 5-HT cells with activated Fos expression were restricted to fewer regions in adults, and the patterns of expression were more consistent across doses. The results reveal dose-dependent effects of nicotine during adolescence with apparent sensitization at different ends of the dosage spectrum examined compared to adults. These data indicate that initial exposure to nicotine may have unique effects in adolescence on the ascending 5-HT system, with the potential for consequences on the affective-motivational qualities of the drug and the subsequent propensity for repeated use.

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

    Shih, Pei-Yu; McIntosh, J. Michael

    2015-01-01

    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

  7. Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

    PubMed Central

    Fowler, Christie D.; Kenny, Paul J.

    2013-01-01

    Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action is considered critical in establishing and maintaining the tobacco smoking habit. Compounds that attenuate nicotine reward are considered promising therapeutic candidates for tobacco dependence, but many of these agents have other actions that limit their potential utility. Nicotine is also highly noxious, particularly at higher doses, and aversive reactions to nicotine after initial exposure can decrease the likelihood of developing a tobacco habit in many first time smokers. Nevertheless, relatively little is known about the mechanisms of nicotine aversion. The purpose of this review is to present recent new insights into the neurobiological mechanisms that regulate avoidance of nicotine. First, the role of the mesocorticolimbic system, so often associated with nicotine reward, in regulating nicotine aversion is highlighted. Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed. Third, the role of the habenular complex in nicotine aversion, primarily medial habenular projections to the interpeduncular nucleus (IPN) but also lateral habenular projections to rostromedial tegmental nucleus (RMTg) and ventral tegmental area (VTA) are reviewed. Forth, brain circuits that are enriched in nAChRs, but whose role in nicotine avoidance has not yet been assessed, will be proposed. Finally, the feasibility of developing novel therapeutic agents for tobacco dependence that act not by blocking nicotine reward but by enhancing nicotine avoidance will be considered. PMID:24055497

  8. 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

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

    PubMed

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

    2007-08-01

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

  10. Unraveling the neurobiology of nicotine dependence using genetically engineered mice.

    PubMed

    Stoker, Astrid K; Markou, Athina

    2013-08-01

    This review article provides an overview of recent studies of nicotine dependence and withdrawal that used genetically engineered mice. Major progress has been made in recent years with mutant mice that have knockout and gain-of-function of specific neuronal nicotinic acetylcholine receptor (nAChR) subunit genes. Nicotine exerts its actions by binding to neuronal nAChRs that consist of five subunits. The different nAChR subunits that combine to compose a receptor determine the distinct pharmacological and kinetic properties of the specific nAChR. Recent findings in genetically engineered mice have indicated that while α4-containing and β2-containing nAChRs are involved in the acquisition of nicotine self-administration and initial stages of nicotine dependence, α7 homomeric nAChRs appear to be involved in the later stages of nicotine dependence. In the medial habenula, α5-containing, α3-containing, and β4-containing nAChRs were shown to be crucially important in the regulation of the aversive aspects of nicotine. Studies of the involvement of α6 nAChR subunits in nicotine dependence have only recently emerged. The use of genetically engineered mice continues to vastly improve our understanding of the neurobiology of nicotine dependence and withdrawal.

  11. 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

  12. The influence of a chronic adolescent nicotine exposure on ethanol withdrawal severity during adulthood in C3H mice.

    PubMed

    Riley, Hugh H; Zalud, André W; Diaz-Granados, Jaime L

    2010-02-01

    Animal and human studies have shown tolerance, consumption, relapse, and behavioral interactions between ethanol and nicotine, but little is understood about their interaction, especially as it relates to ethanol withdrawal in adulthood for subjects who have an adolescent history of using these drugs. This study investigated nicotine's influence on ethanol withdrawal seizures in two different age groups of male C3H mice. Adolescent and adult male C3H mice, beginning at postnatal day 28 or 70, respectively, were subjected to a 7-day chronic exposure to ethanol only, ethanol plus nicotine, nicotine only, or vehicle treatment. Six weeks later, all the groups were subjected to chronic exposure to ethanol vapors and the severity of their ethanol withdrawal seizures was assessed by handling-induced convulsions. An adolescent exposure to chronic nicotine resulted in an exacerbation of ethanol withdrawal seizures in adulthood. Given this, adolescence may contain a neurophysiological critical period that is sensitive to nicotine and which may result in an altered response to ethanol dependency in adulthood. These findings have serious implications for the long-term consequences following co-abuse of these drugs during adolescence.

  13. 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…

  14. Targeting glutamate homeostasis for potential treatment of nicotine dependence

    PubMed Central

    Alasmari, Fawaz; Al-Rejaie, Salim S.; AlSharari, Shakir D.; Sari, Youssef

    2015-01-01

    Several studies demonstrated that impairment in glutamatergic neurotransmission is linked to drug dependence and drug-seeking behavior. Increased extracellular glutamate concentration in mesocorticolimbic regions has been observed in animals developing nicotine dependence. Changes in glutamate release might be associated with stimulatory effect of nicotinic acetylcholine receptors (nAChRs) via nicotine exposure. We and others have shown increased extracellular glutamate concentration, which was associated with downregulation of the major glutamate transporter, glutamate transporter 1 (GLT-1), in brain reward regions of animals exposed to drug abuse, including nicotine and ethanol. Importantly, studies from our laboratory and others showed that upregulation of GLT-1 expression in the mesocorticolimbic brain regions may have potential therapeutic effects in drug dependence. In this review article, we discussed the effect of antagonizing presynaptic nAChRs in glutamate release, the upregulatory effect in GLT-1 expression and the role of glutamate receptors antagonists in the treatment of nicotine dependence. PMID:26589642

  15. 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:…

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

    PubMed

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

    2014-01-01

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

  17. Evaluating nicotine dependence levels in e-cigarette users.

    PubMed

    González Roz, Alba; Secades Villa, Roberto; Weidberg, Sara

    2017-01-11

    Despite the fact that electronic cigarettes (e-cigarettes) are rapidly growing in popularity and use worldwide, there is scarce scientific data on abuse liability among e-cigarette users, and about whether e-cigarette use is related to nicotine dependence or not. The aim of this study is to explore nicotine dependence levels in a sample of experienced e-cigarette users (n= 39) and to compare them with current tobacco cigarette smokers (n=42). We conducted several face-to-face interviews in order to assess sociodemographic and dependence related characteristics in both e-cigarette users and in smokers. Adapted versions of both the Fagerström test for nicotine dependence (FTND) and the nicotine dependence syndrome scale (NDSS) were used to analyze nicotine dependence in each of the groups. Biochemical markers of carbon monoxide and urinary cotinine analysis were also collected. Results showed that e-cigarette users scored lower than cigarette smokers in both FTND and all NDSS subscales. Our findings extend previous research on e-cigarette use and nicotine addiction and suggest that e-cigarette users are less dependent on nicotine than current tobacco cigarette smokers. Further prospective studies are needed to better ascertain their addictiveness potential, comparing those smokers who switched to e-cigarettes from smoking cigarettes, and those who had never been tobacco cigarette smokers.

  18. Nicotine withdrawal among adolescents with acute psychopathology: an item response analysis.

    PubMed

    Strong, David R; Kahler, Christopher W; Ramsey, Susan E; Abrantes, Ana; Brown, Richard A

    2004-06-01

    The present study explored the relationship between psychopathology and the experience of nicotine withdrawal among 191 adolescent smokers deprived of nicotine during a psychiatric hospitalization. Using methods based in item response theory, we demonstrated the ability of symptoms of nicotine withdrawal to cohere in measuring the withdrawal syndrome. After controlling for nicotine dependence, we found that several disorders showed significant but modest univariate relationships with individual withdrawal symptoms. After controlling for comorbidity with other disorders, we found that depressive and conduct disorders maintained significant but modest relationships with increased withdrawal severity. Item analyses across groups suggested that girls, individuals with a depressive disorder, and individuals with a conduct disorder tended to report higher levels of nicotine withdrawal but did not appear to inflate their scores because of disorder- or gender-specific reporting bias. Although levels of acute distress were related to withdrawal severity, the six-item withdrawal index showed good discriminant validity in this sample by demonstrating stronger correlations with craving and level of dependence than could be accounted for by levels of distress alone.

  19. Nicotine dependance among adult male smokers in rural Egypt.

    PubMed

    Gad, Rita R; El-Setouhy, Maged; Haroun, Amany; Gadalla, Shahinaz; Abdel-Aziz, Fatma; Aboul-Fotouh, Aisha; Mohamed, Mostafa K; Mikhail, Nabiel; Israel, Ebenezer

    2003-12-01

    Nicotine dependence is a significant public health problem. This study describes the nicotine dependence status among male adults in rural communities in Egypt. A survey was carried out in five rural villages in Egypt to study the smoking prevalence. A total of 938 current smokers were identified and their nicotine dependence status was studied. About 9% of all smokers in the studied villages were found to have heavy dependence to nicotine. Heavy dependence was associated with younger age of smoking initiation (p<0.05) and more smoking in the first hours of the day (p<0.001). Heavy dependent smokers are less likely to quit smoking (p<0.001), lack the confidence to quit by themselves (p<0.001) and less likely to have tried to quit earlier (p<0.001). Dependent smokers are more likely to smoke in the presence of their children (p<0.001). Reasons for smoking included the habit of smoking helping them to keep them going when tired, to make them alert and not knowing what to do with their hands without a cigarette. The main reasons they identified for restarting smoking after quitting were the signs of withdrawal namely headaches, irritability and difficulty in concentration. Nicotine dependence status and attributes were comparable to studies reported in other countries around the world. Enhanced behavioral and medical intervention strategies are needed to motivate helping both low and heavy nicotine dependent smokers to increase the number and effectiveness of quit attempts.

  20. 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

  1. 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.

  2. 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

  3. Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development

    PubMed Central

    Torres, Oscar V.; Tejeda, Hugo A.; Natividad, Luis A.; O'Dell, Laura E.

    2008-01-01

    This study compared the rewarding and aversive effects of nicotine in adolescent, adult, and adult rats pre-exposed to nicotine during adolescence. Prior to conditioning, the rats were tested for their initial preference for either of 2 distinct compartments. Adolescent and adult rats then received various nicotine doses in their initially non-preferred side on one day and saline in the other side on alternate days. This 2-day procedure was repeated over 8 consecutive days. Following conditioning, rats were re-tested for their preference. Another cohort of adolescent and adult rats were conditioned with various doses of d-amphetamine. Nicotine produced CPP in an inverted U-shaped manner in both age groups. However, adolescents displayed a larger upward shift in CPP that was significant across a wider dose range relative to adults. There were no developmental differences to CPP produced by d-amphetamine. In a final study, adolescents were prepared with pumps that delivered nicotine for 14 days. These rats were conditioned later as adults using the same procedures used previously. Pre-exposure to nicotine during adolescence diminished the aversive effects produced by the highest nicotine dose in naïve adults. Taken together, these studies provide a basis for enhanced vulnerability to nicotine during adolescence. PMID:18571223

  4. Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development.

    PubMed

    Torres, Oscar V; Tejeda, Hugo A; Natividad, Luis A; O'Dell, Laura E

    2008-10-01

    This study compared the rewarding and aversive effects of nicotine in adolescent, adult, and adult rats preexposed to nicotine during adolescence. Prior to conditioning, the rats were tested for their initial preference for either of 2 distinct compartments. Adolescent and adult rats then received various nicotine doses in their initially non-preferred side on one day and saline in the other side on alternate days. This 2-day procedure was repeated over 8 consecutive days. Following conditioning, rats were re-tested for their preference. Another cohort of adolescent and adult rats were conditioned with various doses of D-amphetamine. Nicotine produced CPP in an inverted U-shaped manner in both age groups. However, adolescents displayed a larger upward shift in CPP that was significant across a wider dose range relative to adults. There were no developmental differences to CPP produced by D-amphetamine. In a final study, adolescents were prepared with pumps that delivered nicotine for 14 days. These rats were conditioned later as adults using the same procedures used previously. Pre-exposure to nicotine during adolescence diminished the aversive effects produced by the highest nicotine dose in naive adults. Taken together, these studies provide a basis for enhanced vulnerability to nicotine during adolescence.

  5. Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function.

    PubMed

    Slotkin, Theodore A; Card, Jennifer; Seidler, Frederic J

    2014-03-01

    Nicotine exposure in adolescence produces lasting changes in subsequent behavioral responses to addictive agents. We gave nicotine to adolescent rats (postnatal days PN30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in adulthood (PN90-107), focusing on cerebrocortical serotonin levels and utilization (turnover) as an index of presynaptic activity of circuits involved in emotional state. Our evaluations encompassed responses during the period of adult nicotine treatment (PN105) and withdrawal (PN110, PN120, PN130), as well as long-term changes (PN180). In males, prior exposure to nicotine in adolescence greatly augmented the increase in serotonin turnover evoked by nicotine given in adulthood, an interaction that was further exacerbated during withdrawal. The effect was sufficiently large that it led to significant depletion of serotonin stores, an effect that was not seen with nicotine given alone in either adolescence or adulthood. In females, adolescent nicotine exposure blunted or delayed the spike in serotonin turnover evoked by withdrawal from adult nicotine treatment, a totally different effect from the interaction seen in males. Combined with earlier work showing persistent dysregulation of serotonin receptor expression and receptor coupling, the present results indicate that adolescent nicotine exposure reprograms future responses of 5HT systems to nicotine, changes that may contribute to life-long vulnerability to relapse and re-addiction.

  6. The Importance of Timing of Transitions for Risk of Regular Smoking and Nicotine Dependence

    PubMed Central

    Dierker, Lisa; He, Jianping; Kalaydjian, Amanda; Swendsen, Joel; Degenhardt, Louisa; Glantz, Meyer; Conway, Kevin; Anthony, James; Chiu, Wai Tat; Sampson, Nancy A.; Kessler, Ronald; Merikangas, Kathleen

    2009-01-01

    Purpose To investigate the association between the timing and speed of transition among major smoking milestones (onset, weekly and daily smoking) and onset and recovery from nicotine dependence. Method Analyses are based on data from The National Comorbidity Survey-Replication (NCS-R), a nationally representative face-to-face household survey conducted between February 2001 and April 2003. Results Of those who had ever smoked (n=5,692), 71.3% had reached weekly smoking levels and 67.5% had reached daily smoking. Four in ten who had ever smoked met criteria for nicotine dependence. A shorter time since the onset of weekly and daily smoking was associated with a transition to both daily smoking and nicotine dependence, respectively. The risk for each smoking transition was highest within the year following the onset of the preceding milestone. Recovery was associated with a longer period of time between smoking initiation and the development of dependence and a later age of smoking onset. Conclusions These findings shed light on the clinical course of smoking and nicotine dependence. Given the importance of timing of smoking transitions, prevalence may be further reduced through intervention targeted at adolescents and young adults in the months most proximal to smoking initiation. PMID:18704617

  7. Nicotine produces long-term increases in cocaine reinforcement in adolescent but not adult rats.

    PubMed

    Reed, Stephanie Collins; Izenwasser, Sari

    2017-01-01

    Studies have shown that many smokers begin using nicotine during adolescence, yet the influence of early nicotine use on the response to other drugs of abuse in adulthood is not fully understood. In the current study, nicotine was administered to adolescent and adult rats for seven days. Thirty days later, cocaine-induced locomotor activity and cocaine self-administration were examined when the rats pretreated as adolescents were adults. Rats exposed to nicotine during early adolescence were sensitized thirty days later to the locomotor-activating effects of cocaine and self-administered a greater number of cocaine infusions than adolescent rats pretreated with vehicle. As a result of this increased intake, the cocaine self-administration dose-response curve was shifted upward indicating an increase in cocaine reinforcement. Rats pretreated with nicotine as adults, however, did not show a difference in locomotor activity or cocaine self-administration thirty days later compared to adult rats pretreated with vehicle. These findings suggest that early exposure to nicotine has long-term consequences on cocaine use. These data further suggest that nicotine use may carry a greater risk during adolescence than adulthood and adolescents who smoke may be particularly vulnerable to stimulant use. This article is part of a Special Issue entitled SI: Adolescent plasticity.

  8. Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

    PubMed

    Jackson, Kia J; Sanjakdar, Sarah S; Chen, Xiangning; Damaj, M Imad

    2012-01-01

    The influx of Ca(2+) through calcium-permeable nicotinic acetylcholine receptors (nAChRs) leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB), which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/-) mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

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

    PubMed Central

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

    2010-01-01

    Summary Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient-receptor-potential canonical) channels are defective in response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses. PMID:17081982

  11. Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

    PubMed

    Sudakov, S K; Bogdanova, N G

    2016-10-01

    The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

  12. 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

  13. 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…

  14. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs

    PubMed Central

    Saccone, Scott F.; Hinrichs, Anthony L.; Saccone, Nancy L.; Chase, Gary A.; Konvicka, Karel; Madden, Pamela A.F.; Breslau, Naomi; Johnson, Eric O.; Hatsukami, Dorothy; Pomerleau, Ovide; Swan, Gary E.; Goate, Alison M.; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Martin, Nicholas G.; Montgomery, Grant W.; Wang, Jen C.; Ballinger, Dennis G.; Rice, John P.; Bierut, Laura Jean

    2007-01-01

    Nicotine dependence is one of the world’s leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerström test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the β3 nicotinic receptor subunit gene (P = 9.4 × 10−5). Biologically, the most compelling evidence for a risk variant came from a non-synonymous SNP in the α5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 × 10−4). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies. PMID:17135278

  15. A vaccine for nicotine dependence: targeting the drug rather than the brain.

    PubMed

    Pentel, Paul; Malin, David

    2002-01-01

    Nicotine is the principal addictive component of tobacco. Vaccination of rats against nicotine elicits the production of nicotine-specific antibodies which can bind and sequester nicotine in serum and extracellular fluid, reduce nicotine distribution to brain, and reduce many of nicotine's physiologic and behavioral effects. Vaccination reduces the distribution to brain of both a single nicotine dose and chronic nicotine infusion at rates approximating cigarette smoking. The passive transfer of nicotine-specific antibodies (from vaccinated rabbits) into rats attenuates numerous actions of nicotine: increases in blood pressure and locomotor activity, the induction of nicotine dependence, the relief of nicotine withdrawal by subsequent nicotine and the stimulus properties that allow rats to discriminate a nicotine from a saline injection. Vaccination of rats against nicotine also reduces nicotine-induced dopamine release in the reward pathway of the brain and the reinstatement of nicotine responding, a model for relapse. Because nicotine vaccines target the drug rather than the brain, and the antibodies themselves do not cross the blood-brain barrier, immunization should circumvent the central nervous system side effects that limit the usable dosage of other medications for tobacco dependence. Nicotine vaccines have not yet been tested in humans. The effects of these vaccines in rats are highly dependent upon the concentration of antibody in serum, and are more often partial than complete. If effective for treating tobacco dependence in humans, vaccination will likely benefit from concurrent use of counseling (as is the case with other medications for smoking cessation) and perhaps from its combination with other medications that act via different mechanisms.

  16. Modulation of Hippocampus-Dependent Learning and Synaptic Plasticity by Nicotine

    PubMed Central

    Kenney, Justin W.; Gould, Thomas J.

    2009-01-01

    A long-standing relationship between nicotinic acetylcholine receptors (nAChRs) and cognition exists. Drugs that act at nAChRs can have cognitive-enhancing effects and diseases that disrupt cognition such as Alzheimer’s disease and schizophrenia are associated with altered nAChR function. Specifically, hippocampus-dependent learning is particularly sensitive to the effects of nicotine. However, the effects of nicotine on hippocampus-dependent learning vary not only with the doses of nicotine used and whether nicotine is administered acutely, chronically, or withdrawn after chronic nicotine treatment but also vary across different hippocampus-dependent tasks such as the Morris water maze, the radial arm maze, and contextual fear conditioning. In addition, nicotine has variable effects across different types of hippocampal long-term potentiation (LTP). Because different types of hippocampus-dependent learning and LTP involve different neural and molecular substrates, comparing the effects of nicotine across these paradigms can yield insights into the mechanisms that may underlie the effects of nicotine on learning and memory and aid in understanding the variable effects of nicotine on cognitive processes. This review compares and contrasts the effects of nicotine on hippocampus-dependent learning and LTP and briefly discusses how the effects of nicotine on learning could contribute to nicotine addiction. PMID:18690555

  17. Combined exposure to nicotine and ethanol in adolescent mice differentially affects anxiety levels during exposure, short-term, and long-term withdrawal.

    PubMed

    Abreu-Villaça, Yael; Nunes, Fernanda; do E Queiroz-Gomes, Fabíola; Manhães, Alex C; Filgueiras, Cláudio C

    2008-02-01

    Smoking and consumption of alcoholic beverages are frequently associated during adolescence. This association could be explained by the cumulative behavioral effects of nicotine and ethanol, particularly those related to anxiety levels. However, despite epidemiological findings, there have been few animal studies of the basic neurobiology of the combined exposure in the adolescent brain. In the present work we assessed, through the use of the elevated plus maze, the short- and long-term anxiety effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (from the 30th to the 45th postnatal day) in four groups of male and female C57BL/6 mice: (1) Concomitant NIC (nicotine free-base solution (50 microg/ml) in 2% saccharin to drink) and ETOH (ethanol solution (25%, 2 g/kg) i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) Vehicle. C57BL/6 mice were selected, in spite of the fact that they present slower ethanol metabolism, because they readily consume nicotine in the concentration used in the present study. During exposure (45th postnatal day: PN45), our results indicated that ethanol was anxiolytic in adolescent mice and that nicotine reverted this effect. Short-term drug withdrawal (PN50) elicited sex-dependent effects: exposure to nicotine and/or ethanol was anxiogenic only for females. Although neither nicotine nor ethanol effects persisted up to 1 month postexposure (PN75), the coadministration elicited an anxiogenic response. In spite of the fact that generalizations based on the results from a single strain of mice are prone to shortcomings, our results suggest that the deficient response to the anxiolytic effects of ethanol in adolescents co-exposed to nicotine may drive higher ethanol consumption. Additionally, increased anxiety during long-term smoking and drinking withdrawal may facilitate relapse to drug use.

  18. Combined exposure to nicotine and ethanol in adolescent mice differentially affects memory and learning during exposure and withdrawal.

    PubMed

    Abreu-Villaça, Yael; Medeiros, Ana H; Lima, Carla S; Faria, Felipe P; Filgueiras, Cláudio C; Manhães, Alex C

    2007-07-19

    Human adolescents often associate tobacco smoking and consumption of alcoholic beverages. In spite of this frequent association, little is known about the basic neurobiology of the dual exposure in the adolescent brain. In the present work, we assessed, through the use of the step-through passive avoidance box (2mA, 2s; test-retest interval of 24h), short- and long-term memory/learning effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (postnatal days 30-45: PN30-45) in four groups of male and female C57BL/6 mice: (1) concomitant NIC [nicotine free base solution (50microg/ml) in 2% saccharin to drink] and ETOH [ethanol solution (25%, 2g/kg) i.p. injected every other day] exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. During exposure (PN44-45), deficits in memory/learning due to concomitant NIC+ETOH exposure reflected the summation of the two individual sets of effects. During a short-term drug withdrawal (PN49-50), nicotine improved memory/learning, however, ethanol blocked nicotine-induced improvements. One month post-exposure (PN74-75), a significant female-only improvement in memory/learning was observed as a result of co-administration. In conclusion, our results suggest that detrimental effects of nicotine and ethanol on memory/learning during adolescent combined exposure represent a worsened outcome from the dual exposure. However, negative effects of the combined exposure fail to persist during withdrawal. In fact, the combined exposure elicits a sex-dependent late onset beneficial effect on memory/learning during withdrawal.

  19. Adolescent nicotine alters dendritic morphology in the bed nucleus of the stria terminalis.

    PubMed

    Smith, Kelsey C; Ehlinger, Daniel G; Smith, Robert F

    2015-03-17

    Adolescent nicotine increases dendritic elaboration in several areas associated with the extended amygdala. It also increases anxiety-like behavior in adulthood. An unresolved question is whether adolescent nicotine alters dendritic structure in the bed nucleus of the stria terminalis (BNST), which may contribute to altered anxiety-like behavior. To investigate this possibility, adolescent male Sprague-Dawley rats were administered nicotine (0.5mg/kg/day) 3 days a week for 2 consecutive weeks, starting at postnatal day P (32). 17 days following the end of dosing, brains were processed for Golgi-Cox staining, and neurons were digitally reconstructed in three dimensions. Animals previously treated with nicotine exhibited an increase in the total number of branches and total length of dendrites on BNST neurons. Sholl analysis revealed an increase in the number of intersections with concentric spheres, increased amount of dendritic material within concentric spheres, and an increase of dendritic branching within concentric spheres occurring between 20 and 300 μm from the soma in dendrites. Collectively, our results show that adolescent nicotine alters dendritic structure (by triggering new branch growth), and, by inference, connectivity of the BNST, which may contribute to alterations in behavior induced by adolescent nicotine.

  20. 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.

  1. A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction.

    PubMed

    Weiss, Robert B; Baker, Timothy B; Cannon, Dale S; von Niederhausern, Andrew; Dunn, Diane M; Matsunami, Nori; Singh, Nanda A; Baird, Lisa; Coon, Hilary; McMahon, William M; Piper, Megan E; Fiore, Michael C; Scholand, Mary Beth; Connett, John E; Kanner, Richard E; Gahring, Lorise C; Rogers, Scott W; Hoidal, John R; Leppert, Mark F

    2008-07-11

    People who begin daily smoking at an early age are at greater risk of long-term nicotine addiction. We tested the hypothesis that associations between nicotinic acetylcholine receptor (nAChR) genetic variants and nicotine dependence assessed in adulthood will be stronger among smokers who began daily nicotine exposure during adolescence. We compared nicotine addiction-measured by the Fagerstrom Test of Nicotine Dependence-in three cohorts of long-term smokers recruited in Utah, Wisconsin, and by the NHLBI Lung Health Study, using a candidate-gene approach with the neuronal nAChR subunit genes. This SNP panel included common coding variants and haplotypes detected in eight alpha and three beta nAChR subunit genes found in European American populations. In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity (p = 2.0x10(-5); odds ratio = 1.82; 95% confidence interval 1.39-2.39) in subjects who began daily smoking at or before the age of 16, an exposure period that results in a more severe form of adult nicotine dependence. A substantial shift in susceptibility versus protective diplotype frequency (AA versus BC = 17%, AA versus CC = 27%) was observed in the group that began smoking by age 16. This genetic effect was not observed in subjects who began daily nicotine use after the age of 16. These results establish a strong mechanistic link among early nicotine exposure, common CHRNA5-A3-B4 haplotypes, and adult nicotine addiction in three independent populations of European origins. The identification of an age-dependent susceptibility haplotype reinforces the importance of preventing early exposure to tobacco through public health policies.

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

    PubMed

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

    2016-04-01

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

  3. Adolescents and Adults Differ in the Immediate and Long-Term Impact of Nicotine Administration and Withdrawal on Cardiac Norepinephrine

    PubMed Central

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

    2016-01-01

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

  4. Increased apoptosis and reduced neuronal and glial densities in the hippocampus due to nicotine and ethanol exposure in adolescent mice.

    PubMed

    Oliveira-da-Silva, Andreia; Vieira, Fernanda B; Cristina-Rodrigues, Fabiana; Filgueiras, Cláudio C; Manhães, Alex C; Abreu-Villaça, Yael

    2009-10-01

    It has been recently shown that nicotine and ethanol interact during adolescence affecting memory/learning and anxiety levels. Considering the role of the hippocampus in both anxiety and memory/learning, we investigated whether adolescent nicotine and/or ethanol administration elicit apoptotic cell death and whether this results in neuronal and/or glial density alterations in the following regions of the hippocampus: granular layer of the dentate gyrus (GrDG), molecular layer (Mol), CA1, CA2 and CA3. From the 30th to the 45th postnatal day, C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50mug/ml in 2% saccharin to drink) and ETOH (25%, 2g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We evaluated cell degeneration (TUNEL assay), neuronal and glial densities (optical disector) and region thicknesses at the end of the period of exposure. Our results demonstrate that ETOH elicited an increase in TUNEL-positive cells relative to the vehicle group in all hippocampal regions. NIC elicited less severe region-dependent effects: the number of TUNEL-positive cells was significantly increased in the Mol and CA1 when compared to the vehicle group. These results were paralleled by reductions in neuronal and glial cells densities, which indicate that both cell types are sensitive to the neurotoxic effects of these drugs. There were no effects on region thicknesses. On the other hand, concomitant NIC and ETOH reduced the adverse effects of the drugs when administered separately. This ability of nicotine and ethanol co-exposure to lessen the adverse effects of nicotine and ethanol may contribute to adolescents co-use and co-abuse of tobacco and alcoholic beverages.

  5. Involvement of Glutamatergic and GABAergic Systems in Nicotine Dependence: Implications for Novel Pharmacotherapies for Smoking Cessation

    PubMed Central

    Li, Xia; Semenova, Svetlana; D'Souza, Manoranjan S.; Stoker, Astrid K.; Markou, Athina

    2013-01-01

    Tobacco smoking continues to be a major global health hazard despite significant public awareness of its harmful consequences. Although several treatment options are currently available for smoking cessation, these medications are effective in only a small subset of smokers, and relapse rates continue to be high. Therefore, a better understanding of the neurobiological mechanisms that mediate tobacco dependence is essential for the development of effective smoking cessation medications. Nicotine is the primary psychoactive component of tobacco that drives the harmful tobacco smoking habit. Nicotine binds to nicotinic acetylcholine receptors (nAChRs) in the brain, resulting in the release of a wide range of neurotransmitters, including glutamate and γ-aminobutyric acid (GABA). This review article focuses on the role of the excitatory glutamate system and inhibitory GABA system in nicotine dependence. Accumulating evidence suggests that blockade of glutamatergic transmission or facilitation of GABAergic transmission attenuates the positive reinforcing and incentive motivational aspects of nicotine, inhibits the reward-enhancing and conditioned rewarding effects of nicotine, and blocks nicotine-seeking behavior. Chronic nicotine exposure produced long-term neuroadaptations that contribute to nicotine withdrawal, but the role of GABA and glutamate transmission in nicotine withdrawal is less understood. Overall, the findings presented in this review provide strong converging evidence for the potential effectiveness of glutamatergic and GABAergic medications in nicotine dependence and potentially nicotine withdrawal. PMID:23752091

  6. 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

  7. Low dose nicotine treatment during early adolescence increases subsequent cocaine reward.

    PubMed

    McQuown, Susan C; Belluzzi, James D; Leslie, Frances M

    2007-01-01

    Adolescence is a critical period for the initiation of drug use, starting with tobacco and alcohol and progressing to marijuana and other illicit drugs. These findings have led to the suggestion that tobacco and alcohol are 'gateway' drugs that sensitize maturing reward pathways to the effects of illicit substances such as cocaine. To test this hypothesis, we have examined whether low-dose nicotine pretreatment alters acquisition of cocaine self-administration in adolescents more than in adults. Male and female Sprague-Dawley rats, aged postnatal day (P) 28 or P86, were given two daily intravenous injections of nicotine (0.03 mg/kg/0.1 ml) or saline for 4 days. At P32 and P90, rats were placed in self-administration chambers and tested for acquisition of cocaine (0.2 or 0.5 mg/kg/inj) for 5 days. Data were collapsed across cocaine dose and sex since there was no significant effect of these variables. Adolescent rats pretreated with nicotine exhibited significantly greater cocaine-reinforced responding as compared to saline controls or adults (p<0.01). This drug pretreatment effect did not generalize to all rewards, since nicotine did not increase responding for sucrose pellets in adolescents. These findings provide evidence that the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.

  8. Prenatal nicotine exposure changes natural and drug-induced reinforcement in adolescent male rats.

    PubMed

    Franke, Ryan M; Park, Minjung; Belluzzi, James D; Leslie, Frances M

    2008-06-01

    Clinical studies have demonstrated an increased incidence of substance misuse and obesity in adolescents whose mothers smoked during pregnancy. Although dopamine systems that mediate natural and drug-induced reinforcement have been shown in animal studies to be altered by gestational nicotine treatment, it is not clear whether there are concomitant changes in reinforcement sensitivity. To test whether prenatal nicotine exposure influences sensitivity to natural and drug rewards, timed pregnant rats were implanted with osmotic minipumps delivering saline or nicotine (3 mg/kg/day) from gestational day 4 to 18. Male offspring were tested as adolescents, on postnatal day 32, for operant responding maintained by sucrose pellets or i.v. cocaine (200 or 500 mug/kg per injection). Cocaine-induced stereotypy and c-fos mRNA expression in cortex and striatum were also examined. Complex changes in reward circuitry were observed in the offspring of nicotine-exposed dams. Nicotine-exposed adolescents did not self-administer the low dose of cocaine, but, at the higher dose, exhibited significantly greater cocaine intake and c-fos mRNA expression in nucleus accumbens than did controls. In contrast, control animals showed significantly greater drug-induced stereotypy at both cocaine doses. Operant responding maintained by sucrose was also influenced by gestational nicotine exposure. At a fixed ratio (FR) 1 schedule, although the number of pellets eaten by the two experimental groups was equivalent, more pellets were left uneaten by nicotine-exposed offspring. At FR2 and FR5 schedules, the responding maintained by sucrose pellets was lower in nicotine-exposed offspring. These findings suggest that nicotine exposure during gestation may induce changes in both natural and drug reward pathways.

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

    PubMed

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

    2015-01-01

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

  10. 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

  11. A unique role for striatal serotonergic systems in the withdrawal from adolescent nicotine administration.

    PubMed

    Slotkin, Theodore A; Seidler, Frederic J

    2007-01-01

    Adolescent smokers experience more severe withdrawal symptoms upon smoking cessation than do adults, even when daily smoking has occurred for only a short period or with low levels of consumption. Animal models of nicotine withdrawal indicate involvement of striatal serotonin (5-HT) systems in nicotine reward, withdrawal and craving. We evaluated indices of striatal 5-HT and dopamine (DA) synaptic activity, neurotransmitter levels and turnover (metabolite/transmitter ratio), after continuous nicotine infusions to adolescent rats from postnatal days 30 to 47, using a dose rate (6 mg/kg/day) that produces plasma levels typical of smokers. Withdrawal was accompanied by a significant and persistent loss of striatal 5-HT synaptic activity, evidenced by an initial decline in turnover followed by a reduction in 5-HT content without a compensatory increase in turnover. Similar effects were seen for striatal DA activity. These effects were superimposed on a loss of stimulatory 5-HT cellular responses and promotion of inhibitory responses as identified in an earlier work with this model. None of these alterations was seen during withdrawal in adult rats given the same regimen. The unique adolescent withdrawal effects were not seen when the adolescent nicotine treatment period was shortened to early adolescence (days 30-37), even if the administration paradigm was changed to twice-daily injections to maximize withdrawal stress. Our results are consistent with unique effects of adolescent nicotine withdrawal on striatal 5-HT and DA systems, and point to a potential for serotonin-specific reuptake inhibitors as alternatives to nicotine replacement therapy for smoking cessation in adolescents.

  12. Adolescent exposure to nicotine alters the aversive effects of cocaine in adult rats.

    PubMed

    Hutchison, Mary Anne; Riley, Anthony L

    2008-01-01

    Nicotine is one of the most commonly used drugs in adolescence and has been shown to alter the rewarding effects of cocaine when administered in adulthood. Although the abuse potential of a drug has been suggested to be a balance between its rewarding and aversive effects, the long-term effects of nicotine on the aversive properties of other drugs had not been studied. To that end, in the present study rats exposed to nicotine (0.4 mg/kg) during adolescence (postnatal days 35-44) were tested for the acquisition and extinction of a cocaine-induced conditioned taste aversion (10, 18 or 32 mg/kg) in adulthood. Conditioning consisted of four saccharin-drug pairings followed by six extinction trials. Although cocaine-induced aversions at all doses, no effect of nicotine preexposure was seen during acquisition. During extinction, the nicotine-preexposed groups conditioned with 10 and 18 mg/kg cocaine displayed a decreased rate of extinction compared to their respective controls. These results suggest that while adolescent nicotine exposure does not appear to directly alter the aversive properties of cocaine it may affect other processes related to the response to drugs given in adulthood.

  13. The pharmacological activity of nicotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery.

    PubMed

    Papke, Roger L; Dwoskin, Linda P; Crooks, Peter A

    2007-04-01

    Cigarette smoking and other forms of tobacco use deliver an array of pharmacologically active alkaloids, including nicotine and ultimately various metabolites of these substances. While nornicotine is a significant component in tobacco as well as a minor systemic metabolite of nicotine, nornicotine appears to be N-demethylated locally in the brain where it accumulates at relatively high levels after chronic nicotine administration. We have now examined the effects of nornicotine on specific combinations of neuronal nicotinic acetylcholine receptor (nAChR) subunits expressed in Xenopus oocytes and compared these responses to those evoked by acetylcholine and nicotine. Of the nAChR subtypes studied, we have found that alpha7 receptors are very responsive to nornicotine (EC50 approximately 17 micromol/L I(max) 50%, compared with acetylcholine (ACh)). nAChRs containing the ligand-binding domain of the alpha6 subunits (in the form of an alpha6/alpha3 chimera) are also strongly responsive to nornicotine (EC50 approximately 4 micromol/L I(max) 50%, compared with ACh). Alpha7-type nAChRs have been suggested to be potential therapeutic targets for Alzheimer's disease, schizophrenia and possibly other pathologies. nAChRs containing alpha6 subunits have been suggested to have a role in nicotine-evoked dopamine release. Thus, understanding the actions of nornicotine in the brain may have significance for both emerging therapeutics and the management of nicotine dependence.

  14. Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner

    PubMed Central

    Tejeda, Hugo A.; Natividad, Luis A.; Orfila, James E.; Torres, Oscar V.; O’Dell, Laura E.

    2012-01-01

    Rationale The mechanisms that mediate age differences during nicotine withdrawal are unclear. Objective This study compared kappa opioid receptor (KOR) activation in naïve and nicotine-treated adolescent and adult rats using behavioral and neurochemical approaches to study withdrawal. Methods The behavioral models used to assess withdrawal included conditioned place and elevated plus maze procedures. Deficits in dopamine transmission in the nucleus accumbens (NAcc) were examined using microdialysis procedures. Lastly, the effects of KOR stimulation and blockade on physical signs produced upon removal of nicotine were examined in adults. Results Nicotine-treated adults displayed a robust aversion to an environment paired with a KOR agonist versus naïve adults. Neither of the adolescent groups displayed a place aversion. KOR activation produced an increase in anxiety-like behavior that was highest in nicotine-treated adults versus all other groups. KOR activation produced a decrease in NAcc dopamine that was largest in nicotine-treated adults versus all other groups. Lastly, KOR activation facilitated physical signs of upon removal of nicotine and KOR blockade reduced this effect. Conclusion Chronic nicotine enhanced the affective, anxiogenic, and neurochemical effects produced by KOR activation in adult rats. Our data suggest that chronic nicotine elicits an increase in KOR function, and this may contribute to nicotine withdrawal since KOR activation facilitated and KOR blockade prevented withdrawal signs upon removal of nicotine. Given that chronic nicotine facilitated the neurochemical effects of KOR agonists in adults but not adolescents, it is suggested that KOR regulation of mesolimbic dopamine may contribute to age differences in nicotine withdrawal. PMID:22659976

  15. Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase.

    PubMed

    Xu, Z; Seidler, F J; Cousins, M M; Slikker, W; Slotkin, T A

    2002-10-04

    Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the age at which smoking typically commences. We administered nicotine to adolescent rats via continuous minipump infusions from PN30 to PN47.5, using 6 mg/kg/day, a dose rate that replicates the plasma nicotine levels found in smokers, and examined 5HT receptors and related cell signaling during nicotine administration (PN45) and in the post-treatment period (PN50, 60, 75). Adolescent nicotine decreased 5HT(2) receptor binding in brain regions containing 5HT projections (hippocampus and cerebral cortex), with selectivity for females in the cerebral cortex; regions containing 5HT cell bodies showed either an increase (midbrain in males) or no change (brainstem). In contrast, there were no significant changes in 5HT(1A) receptors; however, the ability of the receptors to signal through adenylyl cyclase (AC) showed a switch from stimulatory to inhibitory effects in females during the post-treatment period. There were also transient alterations in AC responses to beta-adrenergic receptor stimulation, as well as pronounced induction of the AC response to the non-receptor-mediated stimulant, forskolin. Our results indicate that adolescent nicotine exposure alters the concentrations and functions of postsynaptic 5HT receptors in a manner commensurate with impaired 5HT synaptic function. The direction of change, emergence of defects after the cessation of nicotine administration, and sex-preference for effects in females, all support a relationship of impaired 5HT function to the higher incidence of depression seen in adolescent smokers.

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

    PubMed

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

    2015-06-01

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

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

    PubMed

    Glautier, Steven

    2004-06-01

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

  18. 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

  19. Chronic nicotine differentially alters cocaine-induced locomotor activity in adolescent vs. adult male and female rats.

    PubMed

    Collins, Stephanie L; Izenwasser, Sari

    2004-03-01

    Tobacco use is prevalent in the adolescent population. It is a major concern because tobacco is highly addictive and has also been linked to illicit drug use. There is not much research, however, on the interaction between nicotine and other stimulant drugs in animal models of early adolescence. This study examined the effects of chronic nicotine alone and on cocaine-stimulated activity in male and female periadolescent rats compared to male and female adult rats. During the seven-day nicotine pretreatment period, nicotine increased locomotor activity in all groups compared to vehicle controls. Male and female adult rats and female periadolescent rats developed sensitization to the locomotor-activating effects of nicotine over the 7-day treatment period, while male periadolescent rats did not. All groups treated with nicotine, however, exhibited sensitization to nicotine-induced repetitive motion over the 7-day nicotine treatment period. On day 8, male periadolescent rats pretreated with nicotine were more markedly sensitized to the locomotor-activating effects of cocaine than male adult rats, while female rats pretreated with nicotine were not sensitized to cocaine. In contrast, male and female periadolescent rats, but not adult rats, had increased amounts of repetitive beam breaks induced by cocaine after nicotine pretreatment. Overall, it appears that cross-sensitization to cocaine is greater in periadolescent than in adult rats, and that males are more sensitized than females. Thus, it may be that nicotine use during adolescence carries a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of cocaine abuse after nicotine use. This information should be taken into account so as to help us better understand the development of drug addiction in adolescents compared to adults.

  20. 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.

  1. SEX AND OVARIAN HORMONES INFLUENCE VULNERABILITY AND MOTIVATION FOR NICOTINE DURING ADOLESCENCE IN RATS

    PubMed Central

    Lynch, Wendy J.

    2009-01-01

    The purpose of this study was to examine sex differences in sensitivity to nicotine’s reinforcing effects during adolescence, a hormone transition phase characterized by rapid and marked changes in levels of gonadal hormones. Male and female rats were trained to self-administer nicotine (5 or 10 µg/kg/infusion) under a fixed-ratio 1 schedule beginning on postnatal day 30. Following acquisition, responding was assessed under a progressive-ratio schedule until postnatal day 45 with blood sampling occurring prior to the first 5 sessions in order to determine the relationship between gonadal hormones (i.e., estradiol and progesterone in females and testosterone in males) and responding for nicotine. Under low dose conditions, a greater percentage of females than males acquired nicotine self-administration. Under progressive-ratio testing conditions, although adolescent females and males initially responded at similar levels, by the end of the adolescent testing period, females responded at higher levels than males to obtain nicotine infusions. Levels of responding under the progressive-ratio schedule were negatively associated with progesterone and positively associated with the ratio of estradiol to progesterone. These findings demonstrate an enhanced sensitivity in adolescent females as compared to adolescent males to nicotine’s reinforcing effects with evidence implicating circulating hormone levels as modulating this sensitivity. PMID:19619575

  2. Nicotine enhances the cyclic AMP-dependent protein kinase-mediated phosphorylation of alpha4 subunits of neuronal nicotinic receptors.

    PubMed

    Hsu, Y N; Edwards, S C; Wecker, L

    1997-12-01

    Studies determined whether alpha4beta2 or alpha3beta2 neuronal nicotinic receptors expressed in Xenopus oocytes are substrates for cyclic AMP-dependent protein kinase (PKA) and whether nicotine affects receptor phosphorylation. The cRNAs for the subunits were coinjected into oocytes, and cells were incubated for 24 h in the absence or presence of nicotine (50 nM for alpha4beta2 and 500 nM for alpha3beta2 receptors). Nicotine did not interfere with the isolation of the receptors. When receptors isolated from oocytes expressing alpha4beta2 receptors were incubated with [gamma-32P]ATP and the catalytic subunit of PKA, separated by electrophoresis, and visualized by autoradiography, a labeled phosphoprotein with the predicted molecular size of the alpha4 subunit was present. Phosphorylation of alpha4 subunits of alpha4beta2 receptors increased within the first 5 min of incubation with nicotine and persisted for 24 h. In contrast, receptors isolated from oocytes expressing alpha3beta2 receptors did not exhibit a labeled phosphoprotein corresponding to the size of the alpha3 subunit. Results suggest that the PKA-mediated phosphorylation of alpha4 and not alpha3 subunits may explain the differential inactivation by nicotine of these receptor subtypes expressed in oocytes.

  3. 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).

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

    PubMed Central

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

    2015-01-01

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

  5. Mechanism-based medication development for the treatment of nicotine dependence.

    PubMed

    Xi, Zheng-xiong; Spiller, Krista; Gardner, Eliot L

    2009-06-01

    Tobacco use is a global problem with serious health consequences. Though some treatment options exist, there remains a great need for new effective pharmacotherapies to aid smokers in maintaining long-term abstinence. In the present article, we first discuss the neural mechanisms underlying nicotine reward, and then review various mechanism-based pharmacological agents for the treatment of nicotine dependence. An oversimplified hypothesis of addiction to tobacco is that nicotine is the major addictive component of tobacco. Nicotine binds to alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs) located on dopaminergic, glutamatergic and GABAergic neurons in the mesolimbic dopamine (DA) system, which causes an increase in extracellular DA in the nucleus accumbens (NAc). That increase in DA reinforces tobacco use, particularly during the acquisition phase. Enhanced glutamate transmission to DA neurons in the ventral tegmental area appears to play an important role in this process. In addition, chronic nicotine treatment increases endocannabinoid levels in the mesolimbic DA system, which indirectly modulates NAc DA release and nicotine reward. Accordingly, pharmacological agents that target brain acetylcholine, DA, glutamate, GABA, or endocannabonoid signaling systems have been proposed to interrupt nicotine action. Furthermore, pharmacokinetic strategies that alter plasma nicotine availability, metabolism and clearance also significantly alter nicotine's action in the brain. Progress using these pharmacodynamic and pharmacokinetic agents is reviewed. For drugs in each category, we discuss the mechanistic rationale for their potential anti-nicotine efficacy, major findings in preclinical and clinical studies, and future research directions.

  6. 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

  7. In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

    PubMed

    Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

    2017-03-07

    Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence.

  8. Beta 2 subunit-containing nicotinic receptors mediate acute nicotine-induced activation of calcium/calmodulin-dependent protein kinase II-dependent pathways in vivo.

    PubMed

    Jackson, K J; Walters, C L; Damaj, M I

    2009-08-01

    Nicotine is the addictive component of tobacco, and successful smoking cessation therapies must address the various processes that contribute to nicotine addiction. Thus, understanding the nicotinic acetylcholine receptor (nAChR) subtypes and subsequent molecular cascades activated after nicotine exposure is of the utmost importance in understanding the progression of nicotine dependence. One possible candidate is the calcium/calmodulin-dependent protein kinase II (CaMKII) pathway. Substrates of this kinase include the vesicle-associated protein synapsin I and the transcription factor cAMP response element-binding protein (CREB). The goal of these studies was to examine these postreceptor mechanisms after acute nicotine treatment in vivo. We first show that administration of nicotine increases CaMKII activity in the ventral tegmental area (VTA), nucleus accumbens (NAc), and amygdala. In beta2 nAChR knockout (KO) mice, nicotine does not induce an increase in kinase activity, phosphorylated (p)Synapsin I, or pCREB. In contrast, alpha7 nAChR KO mice show nicotine-induced increases in CaMKII activity and pCREB, similar to their wild-type littermates. Moreover, we show that when animals are pretreated with the CaMKII inhibitors 4-[(2S)-2-[(5-isoquinolinylsulfonyl) methylamino]-3-oxo-3-(4-phenyl-1-piperazinyl)propyl]phenyl isoquinolinesulfonic acid ester (KN-62) and N-[2-[[[3-(4-chlorophenyl)-2 propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphonamide (KN-93), nicotine-induced increase in the kinase activity and pCREB was attenuated in the VTA and NAc, whereas pretreatment with (2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, phosphate) (KN-92), the inactive analog, did not alter the nicotine-induced increase in pCREB. Taken together, these data suggest that the nicotine-induced increase in CaMKII activity may correlate with the nicotine-induced increase in pSynapsin I and pCREB in the VTA and NAc via beta2

  9. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

    PubMed Central

    Garcia-Arcos, Itsaso; Geraghty, Patrick; Baumlin, Nathalie; Campos, Michael; Dabo, Abdoulaye Jules; Jundi, Bakr; Cummins, Neville; Eden, Edward; Grosche, Astrid; Salathe, Matthias; Foronjy, Robert

    2016-01-01

    Background The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Methods Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. Results Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. Conclusions Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use. PMID:27558745

  10. 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…

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

    PubMed Central

    Eissenberg, Thomas

    2012-01-01

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

  12. Dependence on tobacco and nicotine products: a case for product-specific assessment.

    PubMed

    Fagerström, Karl; Eissenberg, Thomas

    2012-11-01

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

  13. The effects of nicotine on cognition are dependent on baseline performance.

    PubMed

    Niemegeers, Peter; Dumont, Glenn J H; Quisenaerts, Charel; Morrens, Manuel; Boonzaier, Julia; Fransen, Erik; de Bruijn, Ellen R A; Hulstijn, Wouter; Sabbe, Bernard G C

    2014-07-01

    Since cholinergic neurotransmission plays a major role in cognition, stimulation of the nicotinic acetylcholine receptor may be a target for cognitive enhancement. While nicotine improves performance on several cognitive domains, results of individual studies vary. A possible explanation for these findings is that the effect of nicotine administration may be dependent on baseline cognitive function, where subjects with a suboptimal cognitive performance may benefit from nicotine, while subjects who already perform optimally may show a decline in performance after nicotinic stimulation. We conducted a double-blind randomised placebo-controlled crossover trial, examining the effects of placebo, 1, and 2mg of nicotine on cognition in young (n=16, age 18-30 years) and healthy elderly (n=16, age 60-75 years) subjects. We hypothesised that the elderly would benefit more from nicotine compared to young subjects, as normal ageing is associated with decreases in cognitive function. Attention, working memory, visual memory, information-processing speed, psychomotor function, stereotypy, and emotion recognition were assessed. Compared to the young volunteers, the elderly performed significantly worse on psychomotor function and emotion recognition in the placebo condition. Nicotine had no effect in the young volunteers and decreased performance on working memory and visual memory in the elderly. Contrary to our hypothesis, the effect of nicotine was dependent on baseline performance in both the groups, with subjects with lower baseline performance benefiting from nicotine administration, while those with higher baseline performance performed worse after nicotine administration. This suggests that subjects with lower cognitive performance, irrespective of age, may benefit from nicotine.

  14. A systematic assessment of delay discounting in relation to cocaine and nicotine dependence.

    PubMed

    García-Rodríguez, Olaya; Secades-Villa, Roberto; Weidberg, Sara; Yoon, Jin Ho

    2013-10-01

    Delay discounting is a measure of impulsivity describing how a reinforcer loses value as the delay to its receipt increases. Greater delay discounting is reliably observed among those with different substance use disorders (SUDs) compared to the general population. Nevertheless, the relation between delay discounting and the type and number of substances used remains unclear. The aim of this study was to compare delay discounting across four groups of participants: cocaine- and nicotine-dependent participants, cocaine-dependent only participants, nicotine-dependent only participants, and non-dependent controls. One hundred and seven participants completed a computerized delay discounting task for hypothetical monetary values. Data were fit to Mazur's hyperbolic equation to derive the discounting rate k. Results showed that delay discounting was significantly greater in the cocaine- and nicotine-dependent group, compared to the nicotine-dependent only group, compared to control group. Delay discounting was also greater in the cocaine-dependent only group relative to the nicotine-dependent only and control groups, but no differences were observed between the cocaine- and nicotine-dependent group and the cocaine-dependent only group. This study provides evidence that delay discounting differs depending on the type of SUD but not on the number of SUDs.

  15. Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

    PubMed

    Touiki, Khalid; Rat, Pascal; Arib, Ouafa; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

    2008-05-01

    Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.

  16. Serotonin receptors as potential targets for modulation of nicotine use and dependence.

    PubMed

    Fletcher, Paul J; Lê, Anh Dzung; Higgins, Guy A

    2008-01-01

    Nicotine use carries considerable health risks and plays a major role in a variety of diseases. Current pharmacological treatments to aid in smoking cessation include nicotine-replacement therapy and non-nicotinic strategies such as bupropion and varenicline. While these treatments benefit some individuals there is still a need for better and more effective treatment strategies. Nicotine is the major psychoactive substance in tobacco. Some behavioural effects of nicotine, including its reinforcing efficacy result in part from activation of mesolimbic dopamine neurons. Modulation of dopamine function is one potential treatment strategy that could treat nicotine dependence. Serotonergic neurons modulate the functioning of dopamine neurons in a complex fashion. Much of this complexity arises from the fact that serotonin (5-HT) exerts its effects through multiple receptor subtypes, some of which even act in apparent functional opposition to each other. This article reviews evidence, primarily from animal experiments, using behavioural procedures relevant to nicotine use on the potential for 5-HT receptors as targets for treating nicotine dependence. The 5-HT(1A, 2A, 2C, 3, 4, 6) receptor subtypes have received most experimental attention, with the 5-HT(1A) and 5-HT(2C) receptors being the best studied. Several studies have now shown that 5-HT(1A) receptor antagonists alleviate some of the behavioural signs induced by nicotine withdrawal. Electrophysiological and neurochemical studies show that stimulation of 5-HT(2C) receptors reduces the function of the mesolimbic dopamine pathway. 5-HT(2C) receptor agonists block the stimulatory action of nicotine on midbrain dopamine function. They also reduce several behavioural effects of nicotine including its discriminative stimulus properties and reinforcing effects. Although more work remains to be done, 5-HT(2C) receptor agonists perhaps hold the most promise as potential therapies for smoking cessation.

  17. Effects of maternal separation on nicotine-induced conditioned place preference and subsequent learning and memory in adolescent female rats.

    PubMed

    Dalaveri, Fatemeh; Nakhaee, Nouzar; Esmaeilpour, Khadijeh; Mahani, Saeed Esmaeili; Sheibani, Vahid

    2017-02-03

    Adverse early life experiences can potentially increase risk for drug abuse later in life. However, little research has been conducted studying the effects of maternal separation (MS), an experimental model for early life stress, on the rewarding effects of nicotine. Cognitive function may be affected by MS. So, we also investigated whether nicotine administration affect spatial learning and memory in MS adolescent female rats. Rat pups were subjected to daily MS for 15min (MS15) or 180min (MS180) during the first 2 weeks of life or reared under normal animal facility rearing (AFR) conditions. The place preference test was performed with nicotine (0.6mg/kg,s.c.) or vehicle over a period of 6 conditioning trials during adolescence. Spatial learning and memory performance was evaluated by using Morris water maze (MWM). In our study, adolescent female rats exposed to MS180 shown a significantly greater preference for a nicotine-paired compartment during the testing phase than the MS15 group. Nicotine altered the MS-induced spatial learning defects in the MS180 group. These findings suggest that MS may increase sensitivity to the rewarding effects of nicotine and also it is possible to suggest that nicotine administration may influence learning dysfunction induced by MS in adolescent female rats.

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

    PubMed

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

    2015-09-01

    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.

  19. 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

  20. Exploring the Severity of Dependence Scale (SDS) as a Possible Measure of Nicotine Dependence

    PubMed Central

    Mercincavage, Melissa; Smyth, Joshua M.; Branstetter, Steven A.; Catley, Delwyn

    2015-01-01

    Background The time to first cigarette (TTFC) of the day is an emerging single-item indicator of nicotine dependence due to its robust associations with indices of physical dependence. However, it is unclear if this measure adequately captures other dimensions of dependence. The Severity of Dependence Scale (SDS) is a brief questionnaire used to assess psychological aspects of dependence that has not yet been extensively applied to smoking research. Methods We examined associations between the SDS and TTFC among 255 smokers during the baseline session of a cessation trial. We also examined associations of the SDS and TTFC with biobehavioral dependence indices, quitting behaviors, and cognitive-affective variables, and compared the relative contributions of both measures in predicting these variables. Results TTFC was unrelated to SDS total score, but was related to individual SDS items. TTFC, but not SDS, was correlated with indices of physical dependence (e.g., CPD, CO). Both TTFC and SDS were associated with quitting behaviors, with opposite directionality of associations. TTFC and SDS were both associated with cognitive-affective variables, but SDS outperformed TTFC in strength and number of these relationships. Including both the SDS and TTFC as regression model predictors often increased the amount of variance explained. Conclusions Findings suggest that SDS and TTFC assess different constructs of nicotine dependence; among smokers, the SDS appears to tap into non-physical components of dependence (e.g., loss of control) that relate to quitting motivation and affect. Assessing nicotine dependence using only the SDS may fail to capture physical dependence and, further, may not reflect the same domains of addiction the SDS assesses in other drugs of abuse. Nonetheless, using three SDS items in addition to TTFC may offer utility over using TTFC alone. PMID:26566575

  1. The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment

    PubMed Central

    Elliott, Jennifer C.; Stohl, Malka; Wall, Melanie M.; Keyes, Katherine M.; Goodwin, Renee D.; Skodol, Andrew E.; Krueger, Robert F.; Grant, Bridget F.; Hasin, Deborah

    2014-01-01

    Background and aims Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Design Physical, sexual, and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over three years of follow-up, with and without control for other childhood adversities. Setting National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Participants NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n=1,172) and nicotine dependence (n=4,017). Measurements Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment, and other adverse childhood experiences (e.g., parental divorce). Findings Controlling for demographics only, physical, sexual, and emotional abuse, and physical neglect, predicted three-year persistence of alcohol dependence (adjusted odds ratios [AORs]: 1.50–2.99, 95% CIs 1.04–4.68) and nicotine dependence (AORs: 1.37–1.74, 95% CIs 1.13–2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AORs: 1.53–3.02, 95% CIs 1.07–4.71) and nicotine persistence (AORs: 1.35–1.72, 95% CIs 1.11–2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AORs: 1.19–1.36, 95% CIs 1.11–1.56). Conclusions A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-04-01

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

  4. Nicotine Dependence as a Moderator of a Quitline-Based Message Framing Intervention

    PubMed Central

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

    2010-01-01

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

  5. Nicotine and ethanol interact during adolescence: effects on the central cholinergic systems.

    PubMed

    Ribeiro-Carvalho, Anderson; Lima, Carla S; Filgueiras, Cláudio C; Manhães, Alex C; Abreu-Villaça, Yael

    2008-09-26

    Co-occurrence of tobacco smoking and alcohol consumption during adolescence is frequent and well documented. However, little is known about the basic neurobiology of the combined exposure in the adolescent brain. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChRs), the current work focused on cholinergic systems. From the 30th to the 45th postnatal day (PN), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: 1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; 2) NIC exposure; 3) ETOH exposure; 4) vehicle. We assessed nAChR binding, choline acetyltransferase (ChAT) activity and [3H]hemicholinium-3 (HC-3) binding in the cerebral cortex and midbrain of mice on PN45. In the cortex, ETOH had no effect on nAChRs. In contrast, NIC produced nAChR upregulation while NIC+ETOH elicited a more pronounced effect. In the midbrain, neither ETOH nor NIC had effects on nAChRs. NIC+ETOH, however, elicited a robust nAChR upregulation. Regarding ChAT activity, treatment effects differed between males and females in the cortex. Male NIC mice presented an increase in ChAT. However, ETOH reversed this effect. In contrast, female NIC mice presented decreased ChAT activity. In the midbrain, ETOH increased ChAT. HC-3 binding was not affected. These results indicate that the central cholinergic system is a site at which nicotine and ethanol interact. This interaction might underlie the association between tobacco and alcohol consumption during adolescence.

  6. Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs

    PubMed Central

    Uhl, George R; Liu, Qing-Rong; Drgon, Tomas; Johnson, Catherine; Walther, Donna; Rose, Jed E

    2007-01-01

    Background Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. Results These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms (SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p < 0.00001). Conclusion These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring

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

    PubMed Central

    Ashare, Rebecca L; Schmidt, Heath D

    2014-01-01

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

  8. A new nicotine dependence score and a new scale assessing patient comfort during smoking cessation treatment.

    PubMed

    Issa, Jaqueline Scholz

    2012-01-01

    Smoking is considered the leading preventable cause of morbidity and mortality. The pharmacological management of nicotine withdrawal syndrome enables better cessation rates. In our smoking cessation program, we have developed a data collection system, which includes two new instruments: a score that assesses nicotine dependence in smokers of < 10 cigarettes/day; and a patient comfort scale to be used during smoking cessation treatment. Here, we describe the two instruments, both of which are still undergoing validation.

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

    PubMed

    Alijanpour, S; Rezayof, A

    2013-08-15

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

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

    PubMed Central

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

    2014-01-01

    This study compared nicotine intake and changes in food intake and weight gain in naïve adolescent, naïve adult, and adult rats that were exposed to nicotine during adolescence. An extended intravenous self-administration (IVSA) model was used whereby rats had 23-hour access to saline or increasing doses of nicotine (0.03, 0.06, and 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3-day periods of abstinence. Rats began IVSA as adolescents (PND 32–34) or adults (PND 75). A separate group of rats was exposed to nicotine via osmotic pumps (4.7 mg/kg) for 14 days during adolescence and then began nicotine IVSA as adults (PND 75). The rats that completed the nicotine IVSA regimen were also tested for nicotine-seeking behavior during extinction. The results revealed that nicotine intake was highest in adolescents followed by adults that were pre-exposed to nicotine during adolescence as compared to naïve adults. A similar pattern of nicotine-seeking behavior was observed during extinction. In contrast to nicotine intake, naïve adults displayed robust appetite and weight suppressant effects of nicotine, an effect that was absent in adolescents and adults that were pre-exposed to nicotine during adolescence. Our findings suggest that adolescence is a unique period of enhanced vulnerability to the reinforcing effects of nicotine. Although adolescents gain weight faster than adults, the food intake and weight suppressant effects of nicotine are reduced during adolescence. Importantly, our findings suggest that adolescent nicotine exposure produces long-lasting consequences that enhance nicotine reward and promote tolerance to the anorectic effects of this drug. PMID:24120402

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

    PubMed

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

    2013-11-15

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

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

    PubMed Central

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

    2014-01-01

    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 orthologue of human CYP2A6, by methoxsalen (8-methoxypsoralen) should block nicotine metabolism and decrease its subsequent systemic clearance. Consequently, methoxsalen will alter dependence-related behaviors of nicotine in the mouse. In the first part of the study, a conditioned place preference (CPP) test was used in animals to explore the appetitive reward-like properties of nicotine. In the second part of the study, mice chronically exposed to nicotine were challenged with mecamylamine, a nicotinic antagonist, and tested for physical (somatic and hyperalgesia) and affective (anxiety-related behaviors) precipitated withdrawal signs. The nicotine plasma levels were also measured with or without methoxsalen pretreatment. Methoxsalen (15 and 30 mg/kg, intraperitoneally) pretreatment 15 min before nicotine (0.1 mg/kg, subcutaneously) induced a significant enhancement of nicotine-induced preference in mice (p<0.05). This potentiation was significantly accompanied by an increase in nicotine plasma levels (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 with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs on test day. The potentiation of withdrawal intensity by methoxsalen was accompanied by significant increase in nicotine plasma levels in these mice (p<0.05). Finally, methoxsalen enhanced the ability of nicotine to reverse withdrawal signs in mice undergoing spontaneous withdrawal after chronic nicotine infusion. Spontaneous withdrawal from chronic nicotine administration (36 mg/kg/day in minipumps for 7 days) significantly increased the number of somatic signs and induced

  13. Extended access to nicotine self-administration leads to dependence: Circadian measures, withdrawal measures, and extinction behavior in rats.

    PubMed

    O'Dell, Laura E; Chen, Scott A; Smith, Ron T; Specio, Sheila E; Balster, Robert L; Paterson, Neil E; Markou, Athina; Zorrilla, Eric P; Koob, George F

    2007-01-01

    The present study characterized nicotine intake, circadian patterns of food and water intake, precipitated somatic signs of withdrawal, and extinction of nicotine-seeking behavior in rats with 23-h access to intravenous self-administration (IVSA). Separate groups of animals were allowed access to nicotine IVSA (0.015, n = 9; 0.03, n = 14; 0.06, n = 16; mg/kg/0.1 ml infusion/s; fixed ratio 1) and trained to nosepoke for food and water 23 h/day for 40 consecutive days. Somatic signs of nicotine withdrawal were examined following saline or mecamylamine administration (1.5 mg/kg i.p.), and extinction of nicotine-seeking behavior was assessed. A dose-dependent decrease in lever responding and an increase in nicotine intake were observed, with the highest nicotine dose producing the lowest amount of lever responding and the highest amount of nicotine intake. Nicotine acutely reduced diurnal and nocturnal food intake, producing smaller and fewer meals, and an increased rate of eating. Differences in rate of nicotine intake between the light and dark phase decreased significantly, especially in rats receiving higher unit nicotine doses (0.03 and 0.06 mg/kg), along with long-term decreases in the circadian profile and amplitude of feeding. Mecamylamine precipitated robust withdrawal signs, the magnitude of which was positively correlated with the total amount of self-administered nicotine. Extinction of nicotine-seeking behavior was observed and was facilitated by removal of nicotine-associated cues. The results demonstrate that rats will self-administer nicotine to the point of producing dependence, as measured by somatic signs, resistance to extinction, and measures of food intake.

  14. 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

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

    PubMed

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

    2012-11-01

    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, as 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.

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

    PubMed

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

    2016-02-01

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

  17. Emotion-based impulsivity, smoking expectancies, and nicotine dependence in college students.

    PubMed

    Spillane, Nichea S; Combs, Jessica L; Kahler, Christopher W; Smith, Gregory T

    2013-12-01

    The aim of this study was to enhance our understanding of the relationship between affect-related dispositions to rash action, negative urgency (NU: the tendency to act rashly when in a negative mood), positive urgency (PU: the tendency to act rashly when in a positive mood) and level of nicotine dependence symptoms by examining how the two traits transact with affect-related smoking expectancies. Based on the Acquired Preparedness model of addictive behaviors, we hypothesized that the relationship between PU and level of nicotine dependence would be mediated by positive affect smoking expectancies. We also hypothesized that the relationship between NU and level of nicotine dependence would be mediated by negative affect reduction expectancies. We studied 139 college-aged smokers and found support for this model; positive affect expectancies for smoking mediated the relationship between PU and level of nicotine dependence symptoms. Negative affect reduction smoking expectancies mediated the relationship between NU and level of nicotine dependence. The clinical implications of this research suggest that prevention/intervention programs should include substance-free activities as reinforcement and as ways to deal with extreme positive and negative mood.

  18. The Relationship between Emotional Intelligence and Nicotine Dependence in Lebanese Adults.

    PubMed

    Bou Khalil, R; Chaar, A; Bou Orm, I; Aoun-Bacha, Z; Richa, S

    2017-03-07

    Emotional intelligence (EI) is known to be a risk factor for several types of addiction. The purpose of this study was to investigate, in a cross-sectional design, the presence of a relationship between the level of EI and nicotine dependence in a sample of Lebanese adults. A self-administered questionnaire was used to determine the sociodemographic characteristics, the level of nicotine dependence, and the level of EI in a sample of 142 Lebanese participants from the community. The sample was 51.4% women, with a mean age of 33.9 years. There was no difference in EI level between smokers and non-smokers (p = 0.66), and there were no associations between EI level and the level of nicotine dependence (p = 0.59). However, EI was positively correlated with age (p = 0.023). Due to the fact that smokers have been dependent on nicotine for many years and that EI is known to increase with age, findings suggest that low EI may be a risk factor for initiation, rather than maintenance, of nicotine dependence.

  19. Smoking behavior, nicotine dependency, and motivation to cessation among smokers in the preparation stage of change

    PubMed Central

    Eslami, Ahmad Ali; Charkazi, Abdorrahman; Mostafavi, Firoozeh; Shahnazi, Hossein; Badeleh, Mohammad Taghi; Sharifirad, Gholam Reza

    2012-01-01

    Objective: To investigate selected constructs of the transtheoretical model (TTM) of behavior change regarding smoking behavior among people in the preparation stage, as well as motivation for cessation and nicotine dependency. Methods: A convenience sample of 123 smokers, during between June to and September 2011, completed the Persian version of the short form of a smoking questionnaire based on TTM, the Fagerstrom nicotine dependence test, and the motivational test. Results: Motivation for cessation was great (16.35 ± 2.45). The negative affects of self-efficacy were higher than those to other situations (4.02 ± 0.84). The pros and cons of smoking were 2.69 ± 1.00 and 3.78 ± 0.78, respectively. Temptation was influenced by nicotine dependency (P < 0.05). Early initiation of smoking was significantly associated with severe nicotine dependency (P < 0.05). Conclusion: The results confirm the role of temptation, increase in the cons, decrease in the pros, and nicotine dependency. PMID:23555150

  20. 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

  1. A hierarchical instrumental decision theory of nicotine dependence.

    PubMed

    Hogarth, Lee; Troisi, Joseph R

    2015-01-01

    It is important to characterize the learning processes governing tobacco-seeking in order to understand how best to treat this behavior. Most drug learning theories have adopted a Pavlovian framework wherein the conditioned response is the main motivational process. We favor instead a hierarchical instrumental decision account, wherein expectations about the instrumental contingency between voluntary tobacco-seeking and the receipt of nicotine reward determines the probability of executing this behavior. To support this view, we review titration and nicotine discrimination research showing that internal signals for deprivation/satiation modulate expectations about the current incentive value of smoking, thereby modulating the propensity of this behavior. We also review research on cue-reactivity which has shown that external smoking cues modulate expectations about the probability of the tobacco-seeking response being effective, thereby modulating the propensity of this behavior. Economic decision theory is then considered to elucidate how expectations about the value and probability of response-nicotine contingency are integrated to form an overall utility estimate for that option for comparison with qualitatively different, nonsubstitute reinforcers, to determine response selection. As an applied test for this hierarchical instrumental decision framework, we consider how well it accounts for individual liability to smoking uptake and perseveration, pharmacotherapy, cue-extinction therapies, and plain packaging. We conclude that the hierarchical instrumental account is successful in reconciling this broad range of phenomenon precisely because it accepts that multiple diverse sources of internal and external information must be integrated to shape the decision to smoke.

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

    PubMed

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

    2015-01-01

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

  3. CYP2B6 gene single-nucleotide polymorphisms in an Italian population sample and relationship with nicotine dependence.

    PubMed

    Riccardi, Laura Natalia; Carano, Francesco; Bini, Carla; Ceccardi, Stefania; Ferri, Gianmarco; Pelotti, Susi

    2015-02-01

    The extensively polymorphic CYP2B6 gene metabolizes endogenous and exogenous compounds, among which are nicotine and bupropion, although its contribution to the systemic metabolism of nicotine still remains controversial. In the present study, the distribution of the CYP2B6 variant and genotype frequencies were analyzed in a sample of 202 Italian individuals who were also invited to answer the Fagerström test for nicotine dependence (FTND), in an effort to assess the involvement of CYP2B6 polymorphisms in nicotine dependence. Eight single-nucleotide polymorphisms of CYP2B6 were tested and seven different variants were identified showing frequencies similar to the European population. The reduced activity of the CYP2B6*6 variant was significantly (p=0.025) distributed among the nicotine-dependent individuals compared to non-nicotine dependents. Also, the CYP2B6*1/*6 genotype achieved statistical significance (p=0.016) within the nicotine-dependent individuals. The high occurrence of CYP2B6*6 carriers among nicotine-dependent individuals may suggest a possible involvement in nicotine dependence, with a potential impact on smoking cessation treatments tailored to the individual smoker's genotype.

  4. 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

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

    PubMed

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

    2016-02-01

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

  6. The role of fatty acid amide hydrolase inhibition in nicotine reward and dependence

    PubMed Central

    Muldoon, Pretal P.; Lichtman, Aron H.; Parsons, Loren H.; Damaj, M. Imad

    2012-01-01

    The endogenous cannabinoid anandamide (AEA) exerts the majority of its effects at CB1 and CB2 receptors and is degraded by fatty acid amide hydrolase (FAAH). FAAH KO mice and animals treated with FAAH inhibitors are impaired in their ability to hydrolyze AEA and other non-cannabinoid lipid signaling molecules, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). AEA and these other substrates activate non- cannabinoid receptor systems, including TRPV1 and PPAR-α receptors. In this mini review, we describe the functional consequences of FAAH inhibition on nicotine reward and dependence as well as the underlying endocannabinoid and non-cannabinoid receptor systems mediating these effects. Interestingly, FAAH inhibition seems to mediate nicotine dependence differently in mice and rats. Indeed, pharmacological and genetic FAAH disruption in mice enhances nicotine reward and withdrawal. However, in rats, pharmacological blockade of FAAH significantly inhibits nicotine reward and has no effect in nicotine withdrawal. Studies suggest that non-cannabinoid mechanisms may play a role in these species differences. PMID:22705310

  7. 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…

  8. 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.

  9. 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.

  10. Brain reward system activity in major depression and comorbid nicotine dependence.

    PubMed

    Cardenas, Laura; Tremblay, Lescia K; Naranjo, Claudio A; Herrmann, Nathan; Zack, Martin; Busto, Usoa E

    2002-09-01

    Major depressive disorder (MDD) and nicotine dependence are highly comorbid. MDD patients may use nicotine to ameliorate depressive symptoms. The pathophysiology of the comorbidity of these two disorders is unknown. We hypothesized that a dysfunctional dopaminergic brain reward system (BRS) might be a neurobiological link between MDD and nicotine dependence and that smoking modulates the activity of the BRS by enhancing dopaminergic activity and relieving some depressive symptoms. Eighteen nicotine-dependent, nonmedicated subjects with Diagnostic and Statistical Manual of Mental Disorders (4th edition) diagnosis of MDD and 16 nicotine-dependent, control subjects participated in a double-blind, placebo-controlled, randomized parallel study. A single 30-mg oral dose of d-amphetamine (d-amph) was used to release dopamine and probe the activity of the BRS. The d-amph-mediated physiological and rewarding effects were assessed at baseline and post-treatment using standardized and validated questionnaires. Our results show that d-amph significantly increased blood pressure (p < 0.001). Subjective rewarding d-amph effects increased in both groups. Negative subjective effects were reported while on placebo during nonsmoking sessions. A significant correlation between depression severity (Hamilton depression scale) and d-amph rewarding effects was found in MDD smoker subjects (Addiction Research Center Inventory composite: r = 0.89, p < 0.000; profile of mood states composite: r = 0.71, p < 0.003; and visual analog scales composite: r = 0.78, p < 0.005). These data show that smoking did not modify the response to d-amph in MDD or control subjects, but decreased overall negative mood state during placebo sessions. Severity of depression was significantly correlated with increased rewarding effects of d-amph. Thus, although the BRS may be dysfunctional in MDD subjects, chronic nicotine use does not modify response to d-amph.

  11. 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.

  12. 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…

  13. 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…

  14. Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers

    PubMed Central

    Chenoweth, Meghan J.; Sylvestre, Marie-Pierre; Contreras, Gisele; Novalen, Maria; O’Loughlin, Jennifer; Tyndale, Rachel F.

    2015-01-01

    Background Smoking is influenced by genetic factors including variation in CYP2A6 and CYP2B6, which encode nicotine-metabolizing enzymes. In early adolescence, CYP2A6 slow nicotine metabolism was associated with higher dependence acquisition, but reduced cigarette consumption. Here we extend this work by examining associations of CYP2A6 and CYP2B6 with tobacco dependence acquisition in a larger sample of smokers followed throughout adolescence. Methods White participants from the Nicotine Dependence in Teens cohort that had ever inhaled (n=421) were followed frequently from age 12–18 years. Cox’s proportional hazards models compared the risk of ICD-10 tobacco dependence acquisition (score 3+) for CYP2A6 and CYP2B6 metabolism groups. Early smoking experiences, as well as amount smoked at end of follow-up, was also computed. At age 24 (N=162), we assessed concordance between self-reported cigarette consumption and salivary cotinine. Results In those who initiated inhalation during follow-up, CYP2A6 slow (vs. normal) metabolizers were at greater risk of dependence (hazards ratio (HR)=2.3; 95% CI=1.1, 4.8); CYP2B6 slow (vs. normal) metabolizers had non-significantly greater risk (HR=1.5; 95% CI=0.8, 2.6). Variation in CYP2A6 or CYP2B6 was not significantly associated with early smoking symptoms or cigarette consumption at end of follow-up. At age 24, neither gene was significantly associated with dependence status. Self-reported consumption was associated with salivary cotinine, a biomarker of tobacco exposure, acquired at age 24 (B=0.37; P<0.001). Conclusions Our findings extend previous work indicating that slow nicotine metabolism mediated by CYP2A6, and perhaps CYP2B6, increases risk for tobacco dependence throughout adolescence. PMID:26644138

  15. Beta2-containing nicotinic acetylcholine receptors mediate calcium/calmodulin-dependent protein kinase-II and synapsin I protein levels in the nucleus accumbens after nicotine withdrawal in mice.

    PubMed

    Jackson, Kia J; Imad Damaj, M

    2013-02-15

    Nicotinic acetylcholine receptors are calcium-permeable and the initial targets for nicotine. Studies suggest that calcium-dependent mechanisms mediate some behavioral responses to nicotine; however, the post-receptor calcium-dependent mechanisms associated with chronic nicotine and nicotine withdrawal remain unclear. The proteins calcium/calmodulin-dependent protein kinase II (CaMKII) and synapsin I are essential for neurotransmitter release and were shown to be involved in drug dependence. In the current study, using pharmacological techniques, we sought to (a) complement previously published behavioral findings from our lab indicating a role for calcium-dependent signaling in nicotine dependence and (b) expand on previously published acute biochemical and pharmacological findings indicating the relevance of calcium-dependent mechanisms in acute nicotine responses by evaluating the function of CaMKII and synapsin I after chronic nicotine and withdrawal in the nucleus accumbens, a brain region implicated in drug dependence. Male mice were chronically infused with nicotine for 14 days, and treated with the β2-selective antagonist dihydro-β-erythroidine (DHβE), or the α7 antagonist, methyllycaconitine citrate (MLA) 20min prior to dissection of the nucleus accumbens. Results show that phosphorylated and total CaMKII and synapsin I protein levels were significantly increased in the nucleus accumbens after chronic nicotine infusion, and reduced after treatment with DHβE, but not MLA. A spontaneous nicotine withdrawal assessment also revealed significant reductions in phosphorylated CaMKII and synapsin I levels 24h after cessation of nicotine treatment. Our findings suggest that post-receptor calcium-dependent mechanisms associated with nicotine withdrawal are mediated through β2-containing nicotinic receptors.

  16. 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.

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

    2013-01-01

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

  19. What aspect of dependence does the fagerström test for nicotine dependence measure?

    PubMed

    DiFranza, Joseph R; Wellman, Robert J; Savageau, Judith A; Beccia, Ariel; Ursprung, W W Sanouri A; McMillen, Robert

    2013-01-01

    Although the Fagerström Test for Nicotine Dependence (FTND) and the Heaviness of Smoking Index (HSI) are widely used, there is a uncertainty regarding what is measured by these scales. We examined associations between these instruments and items assessing different aspects of dependence. Adult current smokers (n = 422, mean age 33.3 years, 61.9% female) completed a web-based survey comprised of items related to demographics and smoking behavior plus (1) the FTND and HSI; (2) the Autonomy over Tobacco Scale (AUTOS) with subscales measuring Withdrawal, Psychological Dependence, and Cue-Induced Cravings; (3) 6 questions tapping smokers' wanting, craving, or needing experiences in response to withdrawal and the latency to each experience during abstinence; (4) 3 items concerning how smokers prepare to cope with periods of abstinence. In regression analyses the Withdrawal subscale of the AUTOS was the strongest predictor of FTND and HSI scores, followed by taking precautions not to run out of cigarettes or smoking extra to prepare for abstinence. The FTND and its six items, including the HSI, consistently showed the strongest correlations with withdrawal, suggesting that the behaviors described by the items of the FTND are primarily indicative of a difficulty maintaining abstinence because of withdrawal symptoms.

  20. What Aspect of Dependence Does the Fagerström Test for Nicotine Dependence Measure?

    PubMed Central

    DiFranza, Joseph R.; Wellman, Robert J.; Savageau, Judith A.; Beccia, Ariel; Ursprung, W. W. Sanouri A.; McMillen, Robert

    2013-01-01

    Although the Fagerström Test for Nicotine Dependence (FTND) and the Heaviness of Smoking Index (HSI) are widely used, there is a uncertainty regarding what is measured by these scales. We examined associations between these instruments and items assessing different aspects of dependence. Adult current smokers (n = 422, mean age 33.3 years, 61.9% female) completed a web-based survey comprised of items related to demographics and smoking behavior plus (1) the FTND and HSI; (2) the Autonomy over Tobacco Scale (AUTOS) with subscales measuring Withdrawal, Psychological Dependence, and Cue-Induced Cravings; (3) 6 questions tapping smokers' wanting, craving, or needing experiences in response to withdrawal and the latency to each experience during abstinence; (4) 3 items concerning how smokers prepare to cope with periods of abstinence. In regression analyses the Withdrawal subscale of the AUTOS was the strongest predictor of FTND and HSI scores, followed by taking precautions not to run out of cigarettes or smoking extra to prepare for abstinence. The FTND and its six items, including the HSI, consistently showed the strongest correlations with withdrawal, suggesting that the behaviors described by the items of the FTND are primarily indicative of a difficulty maintaining abstinence because of withdrawal symptoms. PMID:25969829

  1. Ethanol conditioned place preference and alterations in ΔFosB following adolescent nicotine administration differ in rats exhibiting high or low behavioral reactivity to a novel environment.

    PubMed

    Philpot, Rex M; Engberg, Melanie E; Wecker, Lynn

    2014-04-01

    This study determined the effects of adolescent nicotine administration on adult alcohol preference in rats exhibiting high or low behavioral reactivity to a novel environment, and ascertained whether nicotine altered ΔFosB in the ventral striatum (vStr) and prefrontal cortex (PFC) immediately after drug administration or after rats matured to adulthood. Animals were characterized as exhibiting high (HLA) or low (LLA) locomotor activity in the novel open field on postnatal day (PND) 31 and received injections of saline (0.9%) or nicotine (0.56 mg free base/kg) from PND 35 to 42. Ethanol-induced conditioned place preference (CPP) was assessed on PND 68 following 8 days conditioning in a biased paradigm; ΔFosB was measured on PND 43 or PND 68. Following adolescent nicotine exposure, HLA animals demonstrated a CPP when conditioned with ethanol; LLA animals were unaffected. Further, adolescent nicotine exposure for 8 days increased levels of ΔFosB in limbic regions in both HLA and LLA rats, but this increase persisted into adulthood only in LLA animals. Results indicate that adolescent nicotine exposure facilitates the establishment of an ethanol CPP in HLA rats, and that sustained elevations in ΔFosB are not necessary or sufficient for the establishment of an ethanol CPP in adulthood. These studies underscore the importance of assessing behavioral phenotype when determining the behavioral and cellular effects of adolescent nicotine exposure.

  2. 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.

  3. 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

  4. 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.

  5. High-dose nicotine patch therapy for smokers with a history of alcohol dependence: 36-week outcomes.

    PubMed

    Kalman, David; Kahler, Christopher W; Garvey, Arthur J; Monti, Peter M

    2006-04-01

    This study reports findings from an investigation of the efficacy of high-dose nicotine patch (NP) therapy for heavy smokers with a history of alcohol dependence. One hundred thirty participants were randomly assigned to 42 or 21 mg of transdermal nicotine. Follow-up assessments were conducted at 4, 12, 24, and 36 weeks. Differences between dose conditions were nonsignificant, although, unexpectedly, outcomes favored participants in the 21-mg NP condition. Nicotine abstinence rates in the 21- and 42-mg NP conditions on Week 36 follow-up were 16.9% and 9.2%, respectively. Patch condition did not interact with severity of nicotine dependence. However, nicotine abstinence at follow-up was related to a longer length of alcohol abstinence. No evidence was found for better outcomes as a function of the percentage of baseline cotinine replaced by NPs. Future research should focus primarily on investigating ways to improve smoking quit rates for smokers in early alcohol recovery.

  6. 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…

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

    PubMed Central

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

    2015-01-01

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

  8. The effects of strain and prenatal nicotine exposure on ethanol consumption by adolescent male and female rats.

    PubMed

    Berger, David F; Lombardo, John P; Peck, Joshua A; Faraone, Stephen V; Middleton, Frank A; Youngetob, Steven L

    2010-07-11

    Two studies of variables affecting voluntary ethanol consumption by adolescent male and female rats are reported. Sprague-Dawley (SD) and spontaneously hypertensive rats (SHRs) were compared in Experiment 1. Starting on postnatal day 30 all had 24-h access to 2%, then 4%, and then 6% ethanol, followed by 1-h access to the 6% until intake stabilized. During the 1-h access SHR females consumed more ethanol than all other groups. In Experiment 2, the same procedure was used to compare SD groups prenatally exposed to nicotine, with controls. Nicotine-exposed females consumed more ethanol during 1-h access than both nicotine-exposed and control males; but after using water intake as a covariate, the differences were not significant. These data show that deprivation conditions need to be considered when generalizing the results of voluntary consumption studies, and that estrogens may be a modulator of addictive behavior.

  9. Anxiety status affects nicotine- and baclofen-induced locomotor activity, anxiety, and single-trial conditioned place preference in male adolescent rats.

    PubMed

    Falco, Adriana M; McDonald, Craig G; Smith, Robert F

    2014-09-01

    Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety-like behavior on single-trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety-like behavior in rats divided into high-anxiety and low-anxiety groups. Baclofen decreased locomotor behavior in high-anxiety rats. Baclofen alone failed to produce differences in anxiety-like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High- and low-anxiety groups also showed differences in single-trial nicotine-induced place preference. Only high-anxiety rats formed place preference to nicotine, while rats in the low-anxiety group formed no conditioned place preference. These results suggest that among adolescents, high-anxiety individuals are more likely to show preference for nicotine than low-anxiety individuals.

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

    PubMed

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

    2014-10-01

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

  11. Protection genes in nucleus accumbens shell affect vulnerability to nicotine self-administration across isogenic strains of adolescent rat.

    PubMed

    Chen, Hao; Luo, Rui; Gong, Suzhen; Matta, Shannon G; Sharp, Burt M

    2014-01-01

    Classical genetic studies show the heritability of cigarette smoking is 0.4-0.6, and that multiple genes confer susceptibility and resistance to smoking. Despite recent advances in identifying genes associated with smoking behaviors, the major source of this heritability and its impact on susceptibility and resistance are largely unknown. Operant self-administration (SA) of intravenous nicotine is an established model for smoking behavior. We recently confirmed that genetic factors exert strong control over nicotine intake in isogenic rat strains. Because the processing of afferent dopaminergic signals by nucleus accumbens shell (AcbS) is critical for acquisition and maintenance of motivated behaviors reinforced by nicotine, we hypothesized that differential basal gene expression in AcbS accounts for much of the strain-to-strain variation in nicotine SA. We therefore sequenced the transcriptome of AcbS samples obtained by laser capture microdissection from 10 isogenic adolescent rat strains and compared all RNA transcript levels with behavior. Weighted gene co-expression network analysis, a systems biology method, found 12 modules (i.e., unique sets of genes that covary across all samples) that correlated (p<0.05) with amount of self-administered nicotine; 9 of 12 correlated negatively, implying a protective role. PCR confirmed selected genes from these modules. Chilibot, a literature mining tool, identified 15 genes within 1 module that were nominally associated with cigarette smoking, thereby providing strong support for the analytical approach. This is the first report demonstrating that nicotine intake by adolescent rodents is associated with the expression of specific genes in AcbS of the mesolimbic system, which controls motivated behaviors. These findings provide new insights into genetic mechanisms that predispose or protect against tobacco addiction.

  12. 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

  13. Genome-Wide Association for Nicotine Dependence and Smoking Cessation Success in NIH Research Volunteers

    PubMed Central

    Drgon, Tomas; Montoya, Ivan; Johnson, Catherine; Liu, Qing-Rong; Walther, Donna; Hamer, Dean; Uhl, George R

    2009-01-01

    Phenotypes related to both nicotine dependence and ability to successfully quit smoking display substantial heritabilities in classical and molecular genetic studies. Twin studies suggest that some genetic components for dependence overlap with genetic components of ability to quit, but that many components do not overlap. Initial genome-wide association (GWA) studies have demonstrated haplotypes that distinguish nicotine-dependent from nondependent smokers. These haplotypes overlap partially with those that distinguish individuals who successfully quit smoking from those who were not able to quit smoking in clinical trials for smoking cessation. We now report novel genome-wide association results from National Institutes of Health research volunteers who reported smoking histories, symptoms of nicotine dependence, and ability to successfully quit smoking outside the context of a clinical trial. These results buttress data from several prior GWA studies. The data from these volunteers support the idea that previously reported studies of genes associated with smoking cessation success in clinical trial participants may also apply to smokers who are more or less able to initiate and sustain abstinence outside of clinical trial settings. PMID:19009022

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

    PubMed

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

    2008-11-01

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

  15. Stress response dysregulation and stress-induced analgesia in nicotine dependent men and women.

    PubMed

    al'Absi, Mustafa; Nakajima, Motohiro; Grabowski, John

    2013-04-01

    Alterations in the stress response and endogenous pain regulation mechanisms may contribute directly and indirectly to maintenance of nicotine dependence and relapse. We examined the extent to which nicotine dependence alters endogenous pain regulatory systems, including the hypothalamic-pituitary-adrenocortical axis, cardiovascular activity, and stress-induced analgesia. Smokers and nonsmokers attended a laboratory session that included assessment of hormonal and cardiovascular responses to stress. Smokers smoked at their regular rate prior to the session. The hand cold pressor and heat thermal pain tests were completed twice, once after acute stress (public speaking and math tasks) and the other after rest. While smokers and nonsmokers exhibited significant hormonal and cardiovascular responses to stress, smokers exhibited blunted stress responses relative to nonsmokers. They also exhibited diminished stress-induced analgesia. Results demonstrate altered stress response and diminished stress-induced analgesia among chronic smokers, and suggest that these dysregulated physiological responding may contribute to altered endogenous pain regulation.

  16. 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

  17. 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

  18. Calcium-dependent mechanisms of the reinstatement of nicotine-conditioned place preference by drug priming in rats.

    PubMed

    Biala, G; Budzynska, B

    2008-03-01

    Reinstatement of drug-seeking behaviour in animals is relevant to relapse to drug taking in humans. We used the conditioned place preference version of the reinstatement model to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a place preference to the compartment paired with its injections during conditioning (0.5 mg/kg, i.p., three drug sessions). Once established, nicotine place preference was extinguished by repeated training. Following this extinction phase, nicotine-experienced rats were challenged with nicotine (0.5 mg/kg, i.p.), a cannabinoid receptor agonist WIN55,212-2 (0.5 mg/kg, i.p.), ethanol (0.5 g/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). The priming injections of nicotine, WIN55,212-2 and ethanol, but not of d-amphetamine renewed a preference for the compartment previously paired with nicotine. Finally, we examined the influence of the calcium channel antagonists, nimodipine (5 and 10 mg/kg, i.p.) and flunarizine (5 and 10 mg/kg, i.p.), on the reinstatement of nicotine place conditioning induced by WIN55,212-2 and ethanol. It was shown that the calcium channel blockers attenuated the reinstatement of nicotine-conditioned response induced by both drugs. As reinstatement of drug-seeking is a factor for the development of dependence, the L-type calcium channel antagonists may be useful in the relapse-prevention phase of addiction treatment, including cannabinoid, ethanol, and/or nicotine dependence.

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

    PubMed

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

    2015-01-01

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

  20. Exposure to nicotine and ethanol in adolescent mice: effects on depressive-like behavior during exposure and withdrawal.

    PubMed

    Ribeiro-Carvalho, Anderson; Lima, Carla S; Nunes-Freitas, André L; Filgueiras, Cláudio C; Manhães, Alex C; Abreu-Villaça, Yael

    2011-08-01

    Depression and use of addictive substances are two of the most frequent public health problems of adolescents. However, little is known about the association between depression and drug use. Considering that ethanol and nicotine are the most widely used and abused drugs by adolescents, here, we evaluated the depressive-like behavior of C57BL/6 male and female mice exposed to nicotine (NIC) and/or ethanol (ETOH) from the 30th to the 45th (PN30-45) postnatal day. Four groups were analyzed: 1) concomitant NIC (50μg/ml in 2% saccharin to drink) and ETOH (25%, 2g/kg i.p. injected every other day) exposure; 2) NIC exposure; 3) ETOH exposure; 4) vehicle. Immobile behavior, an animal model of depressive behavior, was assessed in the forced swimming test (FST) while the anhedonic state was assessed in the sucrose preference test (SPT) by the end of exposure (PN45-47) as well as during short- (PN50-52) and long-term (PN75-77) withdrawal. In the FST, ETOH female mice showed a reduction in immobility time by the end of exposure while, during long-term withdrawal, immobility time was increased. Short-term withdrawal elicited an increase in immobility time only in female NIC mice. In the SPT, males from both NIC and NIC+ETOH groups showed increased sucrose consumption, suggesting a reward-craving effect during short-term withdrawal. During long-term withdrawal, NIC male mice showed an anhedonic effect. Adolescent nicotine, ethanol and nicotine+ethanol combined exposures during adolescence thus elicit gender-selective effects both during exposure and withdrawal that may contribute to the increased prevalence of depression among drug users.

  1. The reinforcement enhancing effects of nicotine depend on the incentive value of non-drug reinforcers and increase with repeated drug injections.

    PubMed

    Palmatier, Matthew I; Matteson, Gina L; Black, Jessica J; Liu, Xiu; Caggiula, Anthony R; Craven, Laure; Donny, Eric C; Sved, Alan F

    2007-06-15

    We have hypothesized that nicotine has two effects on reinforcement; it increases the probability of responses resulting in nicotine delivery (primary reinforcement) and enhances the apparent reward value of non-nicotine reinforcers (reinforcement enhancing effect). The present studies investigated two predictions generated by this hypothesis: (1) that the reinforcement enhancing effect will depend on apparent stimulus reward value and (2) that the temporal profile of this effect would depend on the pharmacological profile of nicotine. In Experiment 1, rats were trained to lever press for one of two audio-visual stimuli that differed in their intrinsic reinforcing value and then the effect of pre-session nicotine (0.4 mg/kg base) or saline injections was tested. The stimulus that supported very low rates of operant responding displayed smaller increases in responding after pre-session injections of nicotine. In Experiment 2 the effect of nicotine injected 5 min before the session was compared to the effect of nicotine injected 1h after the session using the more reinforcing stimulus condition from the first experiment. A control group received only vehicle injections. In contrast to nicotine injected just prior to the session, post-session injections of nicotine had no detectable effect on responding for the more reinforcing stimulus. These results indicate that the reinforcement enhancing action of nicotine depends on the intensity of the primary reinforcer and that enhanced reinforcement by nicotine depends on coincident access to a stimulus with reinforcing properties.

  2. 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

  3. Nicotine-induced up-regulation and desensitization of alpha4beta2 neuronal nicotinic receptors depend on subunit ratio.

    PubMed

    López-Hernández, Gretchen Y; Sánchez-Padilla, Javier; Ortiz-Acevedo, Alejandro; Lizardi-Ortiz, José; Salas-Vincenty, Janice; Rojas, Legier V; Lasalde-Dominicci, José A

    2004-09-03

    Desensitization induced by chronic nicotine exposure has been hypothesized to trigger the up-regulation of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) in the central nervous system. We studied the effect of acute and chronic nicotine exposure on the desensitization and up-regulation of different alpha4beta2 subunit ratios (1alpha:4beta, 2alpha:3beta, and 4alpha:1beta) expressed in Xenopus oocytes. The presence of alpha4 subunit in the oocyte plasmatic membrane increased linearly with the amount of alpha4 mRNA injected. nAChR function and expression were assessed during acute and after chronic nicotine exposure using a two-electrode voltage clamp and whole-mount immunofluorescence assay along with confocal imaging for the detection of the alpha4 subunit. The 2alpha4:3beta2 subunit ratio displayed the highest ACh sensitivity. Nicotine dose-response curves for the 1alpha4:4beta2 and 2alpha4:3beta2 subunit ratios displayed a biphasic behavior at concentrations ranging from 0.1 to 300 microm. A biphasic curve for 4alpha4:1beta2 was obtained at nicotine concentrations higher than 300 microm. The 1alpha4:4beta2 subunit ratio exhibited the lowest ACh- and nicotine-induced macroscopic current, whereas 4alpha4:1beta2 presented the largest currents at all agonist concentrations tested. Desensitization by acute nicotine exposure was more evident as the ratio of beta2:alpha4 subunits increased. All three alpha4beta2 subunit ratios displayed a reduced state of activation after chronic nicotine exposure. Chronic nicotine-induced up-regulation was obvious only for the 2alpha4: 3beta2 subunit ratio. Our data suggest that the subunit ratio of alpha4beta2 determines the functional state of activation, desensitization, and up-regulation of this neuronal nAChR. We propose that independent structural sites regulate alpha4beta2 receptor activation and desensitization.

  4. Functional Characterization of the α5(Asn398) Variant Associated with Risk for Nicotine Dependence in the α3β4α5 Nicotinic Receptor

    PubMed Central

    Li, Ping; McCollum, Megan; Bracamontes, John; Steinbach, Joe Henry

    2011-01-01

    Smoking is a major cause for premature death. Work aimed at identifying genetic factors that contribute to nicotine addiction has revealed several single nucleotide polymorphisms (SNPs) that are linked to smoking-related behaviors such as nicotine dependence and level of smoking. One of these SNPs leads to an aspartic acid-to-asparagine substitution in the nicotinic receptor α5 subunit at amino acid position 398 [rs16969968; α5(Asn398)]. The α5 subunit is expressed both in the brain and in the periphery. In the brain, it associates with the α4 and β2 subunits to form α4β2α5 receptors. In the periphery, the α5 subunit combines with the α3 and β4 subunits to form the major ganglionic postsynaptic nicotinic receptor subtype. The α3β4α5 receptor regulates a variety of autonomic responses such as control of cardiac rate, blood pressure, and perfusion. In this paradigm, the α5(Asn398) variant may act by regulating autonomic responses that may affect nicotine intake by humans. Here, we have investigated the effect of the α5(Asn398) variant on the function of the α3β4α5 receptor. The wild-type or variant α5 subunits were coexpressed with the α3 and β4 subunits in human embryonic kidney 293 cells. The properties of the receptors were studied using whole-cell and single-channel electrophysiology. The data indicate that the introduction of the α5(Asn398) mutation has little effect on the pharmacology of receptor activation, receptor desensitization, or single-channel properties. We propose that the effect of the α5(Asn398) variant on nicotine use is not mediated by an action on the physiological or pharmacological properties of the α3β4α5 subtype. PMID:21856741

  5. 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.

  6. NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence

    PubMed Central

    Bidwell, L. C.; McGeary, J. E.; Gray, J. C.; Palmer, R.H.C.; Knopik, V.S.; MacKillop, J.

    2014-01-01

    Rationale Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences. The use of intermediate ND phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives (WISDM) represent heavy, pervasive smoking, which is a core feature of nicotine dependence, making these motives strong candidates as intermediate phenotypes. Objective This study examines the WISDM PDM as a novel intermediate phenotype of nicotine dependence. Methods The study used data from 734 European Americans who smoked at least 5 cigs/day [M=16.2 (SD=9.5) cigs/day], completed a phenotypic assessment, and provided a sample of DNA. Based on prior evidence of the role of genetic variation in the NCAM1-TTC12-ANKK1-DRD2 region on chromosome 11q23 in smoking behavior, associations among 12 region loci with nicotine dependence and PDM phenotypes were examined using haplotype and individual loci approaches. In addition, mediational analysis tested the indirect pathway from genetic variation to smoking motives to nicotine dependence. Results NCAM1-TTC12-ANKK1-DRD2 region loci and haplotypes were significantly associated with the motive of Automaticity and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and nicotine dependence. Conclusions These results suggest that motives related to automaticity are a viable intermediate phenotype for understanding genetic contributions to nicotine dependence. Further, NCAM1-TTC12-ANKK1-DRD2 variants may increase the likelihood that a person will become dependent via a highly automatic smoking ritual that can be elicited with little awareness. PMID:25273375

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

    PubMed

    Jackson, Kia J; Damaj, Mohamad I

    2013-12-01

    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 but 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, whereas 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.

  8. [Attitudes of Brazilian pulmonologists toward nicotine dependence: a national survey].

    PubMed

    Viegas, Carlos Alberto de Assis; Valentim, Antonio Gabriel Teles; Amoras, Jaene Andrade Pacheco; Nascimento, Euler Junior Moreira

    2010-01-01

    Smoking is a medical condition, since there is drug dependence, and health professionals should treat it as a chronic disease. In order to understand the attitudes of Brazilian pulmonologists toward smokers, we conducted a national survey, using a questionnaire posted on the Internet, of 2,800 pulmonologists, 587 (21%) of whom completed and returned the questionnaires. We found that 3.2% of the respondents did not believe that smoking is a medical condition. Only 14.7% treated smokers, and 32.4% stated that they would refer smokers to another professional for treatment. These results suggest that Brazilian pulmonologists have insufficient knowledge of smoking cessation therapies.

  9. 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.

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

    PubMed Central

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

    2014-01-01

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

  11. Evaluating psychological markers for human nicotine dependence: tobacco choice, extinction, and Pavlovian-to-instrumental transfer.

    PubMed

    Hogarth, Lee; Chase, Henry W

    2012-06-01

    Individual differences in drug dependence may be mediated by several abnormalities in associative learning, including perseveration of drug-seeking following contingency change, greater control over drug-seeking by Pavlovian stimuli, or greater sensitivity to drug reinforcement establishing higher rates of drug-seeking. To evaluate these three candidate markers for nicotine dependence, Experiment 1 contrasted daily (N = 22) and nondaily smoker groups (N = 22) on a novel instrumental learning task, where one S+ was first trained as a predictor of tobacco reward before being extinguished. Experiment 2 compared daily (N = 18) and nondaily smoker groups (N = 18) on a concurrent-choice task for tobacco and chocolate reward before an extinction test in which the tobacco response was extinguished, followed by a Pavlovian-to-instrumental transfer test, wherein the impact of tobacco and chocolate cues on concurrent choice was measured (gender was balanced within each smoker group). The results showed no group difference in sensitivity to extinction of either the stimulus-drug or response-drug contingency in Experiments 1 and 2, respectively, nor did groups show a difference in Pavlovian-to-instrumental transfer of control over tobacco choice. By contrast, nicotine-dependence status was marked by a higher frequency of tobacco choice in the concurrent-choice procedure, and this choice preference was associated with subjective craving (gender did not affect any behavioral measure). These results favor the view that nicotine dependence in this sample is not determined by individual predilection for perseveration or stimulus-control over drug-seeking, but by greater sensitivity to reinforcement of instrumental drug choice. Value-based decision theories of dependence are discussed.

  12. Simultaneous prenatal ethanol and nicotine exposure affect ethanol consumption, ethanol preference and oxytocin receptor binding in adolescent and adult rats.

    PubMed

    Williams, Sarah K; Cox, Elizabeth T; McMurray, Matthew S; Fay, Emily E; Jarrett, Thomas M; Walker, Cheryl H; Overstreet, David H; Johns, Josephine M

    2009-01-01

    Ethanol consumption and smoking during pregnancy are common, despite the known adverse effects on the fetus. The teratogenicity of each drug independently is well established; however, the effects of concurrent exposure to ethanol and nicotine in preclinical models remain unclear. This study examined the impact of simultaneous prenatal exposure to both ethanol and nicotine on offspring ethanol preference behaviors and oxytocin system dynamics. Rat dams were given liquid diet (17% ethanol derived calories (EDC)) on gestational day (GD) 5 and 35% EDC from GD 6-20 and concurrently an osmotic minipump delivered nicotine (3-6mg/kg/day) from GD 4-postpartum day 10. Offspring were tested for ethanol preference during adolescence (postnatal day (PND) 30-43) and again at adulthood (PND 60-73), followed by assays for oxytocin mRNA expression and receptor binding in relevant brain regions. Prenatal exposure decreased ethanol preference in males during adolescence, and decreased consumption and preference in females during adulthood compared to controls. Oxytocin receptor binding in the nucleus accumbens and hippocampus was increased in adult prenatally exposed males only. Prenatal exposure to these drugs sex-specifically decreased ethanol preference behavior in offspring unlike reports for either drug separately. The possible role of oxytocin in reduction of ethanol consumption behavior is highlighted.

  13. BLOCKING CANNABINOID CB1 RECEPTORS FOR THE TREATMENT OF NICOTINE DEPENDENCE: INSIGHTS FROM PRECLINICAL AND CLINICAL STUDIES

    PubMed Central

    Le Foll, Bernard; Forget, Benoit; Aubin, Henri-Jean; Goldberg, Steven R.

    2009-01-01

    Tobacco use is one of the leading preventable causes of death in developed countries. Since existing medications are only partially effective in treating tobacco smokers, there is a great need for improved medications for smoking cessation. It has been recently proposed that cannabinoid CB1 receptor antagonists represent a new class of therapeutic agents for drug dependence, and, notably, nicotine dependence. Here, we will review current evidence supporting the use of this class of drugs for smoking cessation treatment. Preclinical studies indicate that nicotine exposure produces changes in endocannabinoid content in the brain. In experimental animals, Rimonabant (SR141716) and AM251, two cannabinoid CB1 receptor antagonists, block nicotine self-administration behavior, an effect that may be related to the blockade of the dopamine-releasing effects of nicotine in the brain. Rimonabant also seems efficacious in decreasing the influence of nicotine-associated stimuli over behavior, suggesting that it may act on two distinct neuronal pathways, those implicated in drug-taking behavior and those involved in relapse phenomena. The utility of Rimonabant has been evaluated in several clinical trials. It seems that Rimonabant is an efficacious treatment for smoking cessation, although its efficacy doesn’t exceed that of nicotine replacement therapy and its use may be limited by emotional side effects (nausea, anxiety and depression, mostly). Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of Rimonabant for smoking cessation. PMID:18482433

  14. Sensation seeking, nicotine dependence, and smoking motivation in female and male smokers.

    PubMed

    Carton, S; Jouvent, R; Widlöcher, D

    1994-01-01

    Sensation-seeking scores in female (n = 36) and male (n = 60) French smokers were compared with those for a control group of female (n = 23) and male (n = 45) nonsmokers. The findings clearly show that smokers of both sexes are higher in sensation seeking than their nonsmoking counterparts: they score higher on the Disinhibition, Experience Seeking, and Boredom Susceptibility components of sensation seeking. Smoking women were particularly high on Experience Seeking. The relationships among the sensation-seeking components, nicotine dependence, and motives for smoking were assessed in the smokers. Disinhibition and Experience Seeking moderately correlated with nicotine dependence in females, as assessed by the Fagerström questionnaire and the Addictive factor of the Russell Classification of Smoking by Motives. Women high in Experience Seeking may be at particular risk for smoking and possibly for dependence. Further research is needed to state that the high sensation seeker is a person who might be expected to be particularly sensitive to the stimulating reward of smoking, and thus particularly vulnerable to becoming a dependent smoker.

  15. Impact of Menthol Smoking on Nicotine Dependence for Diverse Racial/Ethnic Groups of Daily Smokers

    PubMed Central

    Soulakova, Julia N.; Danczak, Ryan R.

    2017-01-01

    Introduction: The aims of this study were to evaluate whether menthol smoking and race/ethnicity are associated with nicotine dependence in daily smokers. Methods: The study used two subsamples of U.S. daily smokers who responded to the 2010–2011 Tobacco Use Supplement to the Current Population Survey. The larger subsample consisted of 18,849 non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic (HISP) smokers. The smaller subsample consisted of 1112 non-Hispanic American Indian/Alaska Native (AIAN), non-Hispanic Asian (ASIAN), non-Hispanic Hawaiian/Pacific Islander (HPI), and non-Hispanic Multiracial (MULT) smokers. Results: For larger (smaller) groups the rates were 45% (33%) for heavy smoking (16+ cig/day), 59% (51%) for smoking within 30 min of awakening (Sw30), and 14% (14%) for night-smoking. Overall, the highest prevalence of menthol smoking corresponded to NHB and HPI (≥65%), followed by MULT and HISP (31%–37%), and then by AIAN, NHW, and ASIAN (22%–27%) smokers. For larger racial/ethnic groups, menthol smoking was negatively associated with heavy smoking, not associated with Sw30, and positively associated with night-smoking. For smaller groups, menthol smoking was not associated with any measure, but the rates of heavy smoking, Sw30, and night-smoking varied across the groups. Conclusions: The diverse associations between menthol smoking and nicotine dependence maybe due to distinction among the nicotine dependence measures, i.e., individually, each measure assesses a specific smoking behavior. Menthol smoking may be associated with promoting smoking behaviors. PMID:28085040

  16. 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

  17. 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

  18. The effects of message framing, involvement, and nicotine dependence on anti-smoking public service announcements.

    PubMed

    Jung, Wan S; Villegas, Jorge

    2011-01-01

    Anti-smoking Public Service Announcements (PSAs) typically emphasize the negative consequences of failing to quit smoking (negative frame), as opposed to emphasizing the benefits of quitting (positive frame). However, stressing the benefits of quitting sometimes produces better communication outcomes. Previous research on message framing has tried to identify factors affecting the impact of positive framing and negative framing. Data were collected on 188 undergraduates attending a southeastern university in the United States who were assigned randomly to view either positive or negative messages. Our study found that involvement and nicotine dependence moderated the impact of framed smoking-cessation messages on attitude toward the ad.

  19. 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

  20. Nicotine Dependence

    MedlinePlus

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  1. 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

  2. Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats.

    PubMed

    Natividad, Luis A; Tejeda, Hugo A; Torres, Oscar V; O'Dell, Laura E

    2010-02-01

    The behavioral effects of nicotine withdrawal are lower in adolescent versus adult rats. However, the neurochemical mechanisms that mediate these developmental differences are unknown. Previous studies have shown that extracellular levels of dopamine in the nucleus accumbens (NAcc) are reduced in adult rats experiencing withdrawal. This study compared dopamine levels in the NAcc of male adolescent and adult rats experiencing nicotine withdrawal. Animals were prepared with subcutaneous pumps that delivered an equivalent nicotine dose in these age groups. Following 13 days of nicotine exposure, rats were implanted unilaterally with microdialysis probes into the NAcc and ipsilateral ventral tegmental area (VTA). The next day, dialysate levels were collected following systemic administration of the nicotinic-receptor antagonist mecamylamine to precipitate withdrawal. Mecamylamine produced an average % decrease in NAcc dopamine that was lower in adolescents (20%) versus adults (44%). Similar developmental differences were observed with the dopaminergic (DOPAC and HVA) but not serotonergic (5-HIAA) metabolites. A follow-up study compared NAcc dopamine in adolescent and adult rats receiving intra-VTA administration of bicuculline, which reduces gamma-aminobutyric acid (GABA) inhibition of dopamine transmission. The results revealed that blockade of GABA(A) receptors in the VTA produced a two-fold increase in NAcc dopamine of adults but not adolescents. These results provide a potential mechanism involving dopamine that mediates developmental differences in nicotine withdrawal. Specifically, they suggest that GABA systems are underdeveloped during adolescence and this reduced inhibition of dopamine neurons in the VTA may lead to reduced decreases in NAcc dopamine of young animals experiencing withdrawal.

  3. Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats

    PubMed Central

    Natividad, Luis A.; Tejeda, Hugo A.; Torres, Oscar V.; O’Dell, Laura E.

    2010-01-01

    The behavioral effects of nicotine withdrawal are lower in adolescent versus adult rats. However, the neurochemical mechanisms that mediate these developmental differences are unknown. Previous studies have shown that extracellular levels of dopamine in the nucleus accumbens (NAcc) are reduced in adult rats experiencing withdrawal. This study compared dopamine levels in the NAcc of male adolescent and adult rats experiencing nicotine withdrawal. Animals were prepared with subcutaneous pumps that delivered an equivalent nicotine dose in these age groups. Following 13 days of nicotine exposure, rats were implanted unilaterally with microdialysis probes into the NAcc and ipsilateral ventral tegmental area (VTA). The next day, dialysate levels were collected following systemic administration of the nicotinic-receptor antagonist mecamylamine to precipitate withdrawal. Mecamylamine produced an average % decrease in NAcc dopamine that was lower in adolescents (20%) versus adults (44%). Similar developmental differences were observed with the dopaminergic (DOPAC and HVA) but not serotonergic (5-HIAA) metabolites. A follow up study compared NAcc dopamine in adolescent and adult rats receiving intra-VTA administration of bicuculline, which reduces gamma-aminobutyric acid (GABA) inhibition of dopamine transmission. The results revealed that blockade of GABAA receptors in the VTA produced a 2-fold increase in NAcc dopamine of adults but not adolescents. These results provide a potential mechanism involving dopamine that mediates developmental differences in nicotine withdrawal. Specifically, they suggest that GABA systems are underdeveloped during adolescence and this reduced inhibition of dopamine neurons in the VTA may lead to reduced decreases in NAcc dopamine of young animals experiencing withdrawal. PMID:19771590

  4. Effects of adolescent methamphetamine and nicotine exposure on behavioral performance and MAP-2 immunoreactivity in the nucleus accumbens of adolescent mice.

    PubMed

    Buck, Jordan M; Morris, Alysse S; Weber, Sydney J; Raber, Jacob; Siegel, Jessica A

    2017-04-14

    The neurotoxic effects of methamphetamine (MA) exposure in the developing and adult brain can lead to behavioral alterations and cognitive deficits in adults. Previous increases in the rates of adolescent MA use necessitate that we understand the behavioral and cognitive effects of MA exposure during adolescence on the adolescent brain. Adolescents using MA exhibit high rates of nicotine (NIC) use, but the effects of concurrent MA and NIC in the adolescent brain have not been examined, and it is unknown if NIC mediates any of the effects of MA in the adolescent. In this study, the long-term effects of a neurotoxic dose of MA with or without NIC exposure during early adolescence (postnatal day 30-31) were examined later in adolescence (postnatal day 41-50) in male C57BL/6J mice. Effects on behavioral performance in the open field, Porsolt forced swim test, and conditioned place preference test, and cognitive performance in the novel object recognition test and Morris water maze were assessed. Additionally, the effects of MA and/or NIC on levels of microtubule associated-2 (MAP-2) protein in the nucleus accumbens and plasma corticosterone were examined. MA and NIC exposure during early adolescence separately decreased anxiety-like behavior in the open field test, which was not seen following co-administration of MA/NIC. There was no significant effect of early adolescent MA and/or NIC exposure on the intensity of MAP-2 immunoreactivity in the nucleus accumbens or on plasma corticosterone levels. These results show that early adolescent MA and NIC exposure separately decrease anxiety-like behavior in the open field, and that concurrent MA and NIC exposure does not induce the same behavioral change as either drug alone.

  5. Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving

    PubMed Central

    Coen, Kathleen; Tamadon, Sahar; Hope, Bruce T.; Shaham, Yavin; Lê, A.D.

    2016-01-01

    The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. We trained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos–lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased “incubated” nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation. SIGNIFICANCE STATEMENT The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. It is currently unknown whether incubation of craving

  6. 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

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

    ERIC Educational Resources Information Center

    Zelman, Diane C.; And Others

    1992-01-01

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

  8. 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

    2013-06-07

    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.

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

    PubMed

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

    2007-05-01

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

  10. Nicotine dependence produces hyperalgesia: role of corticotropin-releasing factor-1 receptors (CRF1Rs) in the central amygdala (CeA).

    PubMed

    Baiamonte, Brandon A; Valenza, Marta; Roltsch, Emily A; Whitaker, Annie M; Baynes, Brittni B; Sabino, Valentina; Gilpin, Nicholas W

    2014-02-01

    Because tobacco use has a large negative health and financial impact on society, it is critical to identify the factors that drive excessive use. These factors include the aversive withdrawal symptoms that manifest upon cessation of tobacco use, and may include increases in nociceptive processing. Corticotropin-releasing factor (CRF) signalling in the central amygdala (CeA) has been attributed an important role in: (1) central processing of pain, (2) excessive nicotine use that results in nicotine dependence, and (3) in mediating the aversive symptoms that manifest following cessation of tobacco exposure. Here, we describe three experiments in which the main hypothesis was that CRF/CRF1 receptor (CRF1R) signalling in the CeA mediates nicotine withdrawal-induced increases in nociceptive sensitivity in rats that are dependent on nicotine. In Experiment 1, nicotine-dependent rats withdrawn from chronic intermittent (14-h/day) nicotine vapor exhibited decreased hind paw withdrawal latencies in response to a painful thermal stimulus in the Hargreaves test, and this effect was attenuated by systemic administration of the CRF1R antagonist, R121919. In Experiment 2, nicotine-dependent rats withdrawn from nicotine vapor exhibited robust increases in mRNA for CRF and CRF1Rs in CeA. In Experiment 3, intra-CeA administration of R121919 reduced thermal nociception only in nicotine-dependent rats. Collectively, these results suggest that nicotine dependence increases CRF/CRF1R signalling in the CeA that mediates withdrawal-induced increases in sensitivity to a painful stimulus. Future studies will build on these findings by exploring the hypothesis that nicotine withdrawal-induced reduction in pain thresholds drive excessive nicotine use via CRF/CRF1R signalling pathways.

  11. L-type calcium channels and calcium/calmodulin-dependent kinase II differentially mediate behaviors associated with nicotine withdrawal in mice.

    PubMed

    Jackson, K J; Damaj, M I

    2009-07-01

    Smoking is a widespread health problem. Because the nicotine withdrawal syndrome is a major contributor to continued smoking and relapse, it is important to understand the molecular and behavioral mechanisms of nicotine withdrawal to generate more effective smoking cessation therapies. Studies suggest a role for calcium-dependent mechanisms, such as L-type calcium channels and calcium/calmodulin-dependent protein kinase II (CaMKII), in the effects of nicotine dependence; however, the role of these mechanisms in nicotine-mediated behaviors is unclear. Thus, the goal of this study was to elucidate the role of L-type calcium channels and CaMKII in nicotine withdrawal behaviors. Using both pharmacological and genetic methods, our results show that L-type calcium channels are involved in physical, but not affective, nicotine withdrawal behaviors. Although our data do provide evidence of a role for CaMKII in nicotine withdrawal behaviors, our pharmacological and genetic assessments yielded different results concerning the specific role of the kinase. Pharmacological data suggest that CaMKII is involved in somatic signs and affective nicotine withdrawal, and activity level is decreased after nicotine withdrawal, whereas the genetic assessments yielded results suggesting that CaMKII is involved only in the anxiety-related response, yet the kinase activity may be increased after nicotine withdrawal; thus, future studies are necessary to clarify the precise behavioral specifics of the relevance of CaMKII in nicotine withdrawal behaviors. Overall, our data show that L-type calcium channels and CaMKII are relevant in nicotine withdrawal and differentially mediate nicotine withdrawal behaviors.

  12. Treating nicotine dependence during pregnancy and postpartum: understanding clinician knowledge and performance.

    PubMed

    Bonollo, Debra P; Zapka, Jane G; Stoddard, Anne M; Ma, Yunsheng; Pbert, Lori; Ockene, Judith K

    2002-12-01

    This study investigated the relationship of clinicians' knowledge of treatments for nicotine dependence during pregnancy and postpartum and explored what provider characteristics are associated with knowledge levels. Survey data from community health center (CHC)-based prenatal, pediatric (PED), and WIC program (Special Supplemental Nutrition Program for Women, Infants, and Children) providers participating in a randomized clinical study were used. Providers reported low awareness of the health risks of smoking to the developing fetus/child of pregnant and postpartum women and of the effectiveness of nicotine replacement therapy (NRT) for doubling quit rates. Obstetric (OB) and WIC providers were more aware than PED providers that provider-delivered interventions are effective. Confidence in using counseling steps was significantly associated with general and NRT-related knowledge. NRT-related knowledge, but not general knowledge, was associated with higher performance of intervention steps. Educational programs targeting OB, WIC, and PED providers' knowledge about effective smoking cessation counseling strategies and their confidence in being effective with patients are needed.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. 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

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

    PubMed

    Webster, J C; Francis, M M; Porter, J K; Robinson, G; Stokes, C; Horenstein, B; Papke, R L

    1999-07-01

    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.

  17. Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions.

    PubMed

    Berg, Sarah A; Sentir, Alena M; Cooley, Benjamin S; Engleman, Eric A; Chambers, R Andrew

    2014-11-01

    Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction. Neonatal ventral hippocampal lesions (NVHL) have previously been demonstrated to produce post-adolescent-onset, pharmacological, neurobiological and cognitive-deficit features of schizophrenia. Here, we show that NVHLs increase adult nicotine self-administration, potentiating acquisition-intake, total nicotine consumed and drug seeking. Behavioral sensitization to nicotine in adolescence prior to self-administration is not accentuated by NVHLs in contrast to increased nicotine self-administration and behavioral sensitization documented in adult NVHL rats, suggesting periadolescent neurodevelopmental onset of nicotine addiction vulnerability in the NVHL model. Delivering a nicotine regimen approximating the exposure used in the sensitization and self-administration experiments (i.e. as a treatment) to adult rats did not specifically reverse NVHL-induced cortical-hippocampal-dependent cognitive deficits and actually worsened cognitive efficiency after nicotine treatment stopped, generating deficits that resemble those due to NVHLs. These findings represent the first prospective evidence demonstrating a causal link between disease processes in schizophrenia and nicotine addiction. Developmental cortical-temporal limbic dysfunction in mental illness may thus amplify nicotine's reinforcing effects and addiction risk and severity, even while producing cognitive deficits that are not

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

    PubMed Central

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

    2015-01-01

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

  19. 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

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

    PubMed

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

    2013-03-13

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

  1. Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

    PubMed

    Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

    2016-05-01

    Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

  2. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction.

    PubMed

    Christensen, Mark H; Ishibashi, Masaru; Nielsen, Michael L; Leonard, Christopher S; Kohlmeier, Kristi A

    2014-10-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine induced larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age.

  3. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

    PubMed Central

    Christensen, Mark H.; Ishibashi, Masaru; Nielsen, Michael L.; Leonard, Christopher S.; Kohlmeier, Kristi A.

    2015-01-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age. PMID:24863041

  4. 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

  5. [Clinical intervention of nicotine dependence from a systemic-relational focus. Results of a descriptive study of series of cases].

    PubMed

    Fuentes-Pila, José María; López García, Esther; Calatayud, Pedro; Pereira, Roberto

    2007-01-01

    We present in this work a descriptive study of series of cases in treatment for nicotine addiction with a multicomponent program focusing on a systemic-relational therapy. While a good number of smokers are able to stop smoking, with the help of different programs with different levels of complexity depending on their level of addiction, there is a group of smokers who associate their difficulty to stop smoking with aspects related to their life cycle situation, problems with their family of origin or with their social network. We revised the most relevant clinical aspects of the model and presented the results of a descriptive study of a series of 128 patients, of wich 60.50% expressed family and/or personal problems that made the possibilities of success in the program more difficult. After an intervention that lasted a year during wich there were 25 therapy sessions together with combined substitute therapy with nicotine (STN) during the first 3 months of treatment, 77.30% maintained abstinence. Nowadays we know much more about nicotine addictions, giving different answers to different needs, just like the different levels of complexity of each addict. We consider that the contributions of the systemic-relational model in its different ways of understanding the intervention, can better the results of the treatment. We are justified in increasing the level of complexity of the interventions when there exist complications in the clinical handling of nicotine addiction because of other models of treatment of lesser intensity.

  6. 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.

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

    PubMed Central

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

    2007-01-01

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

  8. Electroacupuncture Therapy in Nicotine Dependence: A Double Blind, Sham-Controlled Study

    PubMed Central

    BİLİCİ, Mustafa; GÜVEN, Sertaç; KÖŞKER, Selcen; ŞAFAK, Ayşe; SEMİZ, Ümit Başar

    2016-01-01

    Introduction The number of non-pharmacological controlled studies is insufficient in the treatment of nicotine dependence (ND). Nevertheless, non-pharmacological treatments, such as electroacupuncture (EA), are becoming increasingly popular in the treatment of ND. The aims of this study were to determine the efficacy and safety of “true EA therapy” (TEAT) compared to those of “sham EA therapy” (SEAT) in ND treatment. Methods Eligible patients who met the DSM-IV criteria for ND (n=450) were included in the study. This study was a double-blinded, sham-controlled clinical trial with a 4-week treatment period and 4-week follow-up conducted between June and December 2009 at a psychiatry outpatient clinic. One hundred and sixty four adult (≥18 years; 44 men, 120 women) cigarette smokers out of 450 patients who met the inclusion and exclusion criteria were enrolled in the study in a ratio of 1:1 to receive TEAT (n=84) or SEAT (n=80). Routine biochemical and hematological tests, chest X-Ray, and ECG were carried out; end-expired carbon monoxide (CO) levels were measured too. Clinical characteristics were obtained through the Fagerström Nicotine Dependence Test (FNDT), Hamilton Rating Scale for Depression (HRSD), and Hamilton Anxiety Scale (HAS). EA was carried out by a trademark device, Antismoke 3000®. Efficacy analyses were performed on “intent-to-treat analysis.” Primary outcome was the differences from baseline to endpoint in mean FNDT, number of cigarettes smoked per day, and CO levels at week 4. Secondary outcomes were the same variables at week 8. These variables were assessed via analysis of covariance (ANCOVA). Results Mean baseline FNDT, HRSD, HAS, and CO levels of the groups were statistically similar. TEAT and SEAT groups demonstrated no significant changes in the outcome variables and smoking cessation rates (35.7% and 30%, respectively). Of those remaining outside of the study, 8.3% were from the TEAT group and 8.7% were from the SEAT group

  9. ACUTE NEGATIVE AFFECT RELIEF FROM SMOKING DEPENDS ON THE AFFECT SITUATION AND MEASURE, BUT NOT ON NICOTINE

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.; Conklin, Cynthia A.; Sayette, Michael A.; Giedgowd, Grace E.

    2017-01-01

    Background Smoking acutely relieves negative affect (NA) due to smoking abstinence but may not relieve NA from other sources, such as stressors. Methods Dependent smokers (N=104) randomly assigned to one of three smoking conditions (nicotine or denic cigarettes, or no smoking) completed four negative mood induction procedures (one per session): 1) overnight smoking abstinence, 2) challenging computer task, 3) public speech preparation, and 4) watching negative mood slides. A fifth session involved a neutral mood control. The two smoking groups took 4 puffs on their assigned cigarette, and then smoked those same cigarettes ad libitum during continued mood induction. All subjects rated their level of NA and positive affect (PA) on several measures (Mood Form, PANAS, Stress-Arousal Checklist, and STAI-state). They also rated craving and withdrawal. Results NA relief from smoking depended on the NA source (i.e. mood induction procedure) and the affect measure. Smoking robustly relieved NA due to abstinence on all 4 measures, but only modestly relieved NA due to the other sources and typically on only some measures. Smoking’s effects on PA and withdrawal were similar to effects on NA, but relief of craving depended less on NA source. Smoking reinforcement only partly matched the pattern of NA relief. Few responses differed between the nicotine and denic smoking groups. Conclusions Acute NA relief from smoking depends on the situation and the affect measure used but may not depend on nicotine intake. These results challenge the common assumption that smoking, and nicotine in particular, broadly alleviates NA. PMID:20132927

  10. [Prevention of beer dependence in adolescents in educational institutions].

    PubMed

    Solov'ev, A G; Novikova, G A

    2013-01-01

    The authors have systematized approaches to the prevention of beer dependence in adolescents and presented the inner structure of prevention in educational institutions in terms of consecutive steps. The author's methods for adolescence beer dependence diagnosis are described. Different forms of preventive work with adolescences and their parents allowing to combine flexibly the preventive methods with the participation of cross-functional specialists are presented.

  11. Hippocampal increased cell death and decreased cell density elicited by nicotine and/or ethanol during adolescence are reversed during drug withdrawal.

    PubMed

    Oliveira-da-Silva, A; Manhães, A C; Cristina-Rodrigues, F; Filgueiras, C C; Abreu-Villaça, Y

    2010-04-28

    We have recently identified hippocampal cell death and reduced neuronal and glial cells densities during adolescent nicotine and ethanol exposures and outcomes reduced in severity when nicotine and ethanol are co-administered during this developmental period. In the present study, we investigated the effects of adolescent nicotine and/or ethanol withdrawal on the following regions of the hippocampus: Granular layer of the Dentate Gyrus (GrDG), Molecular layer (Mol), CA1, CA2 and CA3. From the 30th to the 45th postnatal day (PN30-PN45), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We evaluated cell degeneration (TUNEL assay), neuronal and glial densities (optical Disector) and region thicknesses two (PN47) and five (PN50) days post-exposure. On PN47, there were increases in the number of TUNEL+ cells in most hippocampal regions of both ETOH and NIC groups. In the NIC+ETOH group there were less severe effects. These results were paralleled by reductions in neuronal and glial cells densities for all treatment groups. In contrast, on PN50, ethanol and/or nicotine withdrawal were associated with compensatory reductions in TUNEL+ cells in all hippocampal regions. These results were paralleled by a reversal of effects on neuronal and glial densities so that there were no longer differences between groups. There were no effects on region thicknesses. These results suggest that deleterious effects of nicotine and/or ethanol are reversed during prolonged withdrawal.

  12. 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

  13. Clinical Considerations in the Assessment of Adolescent Chemical Dependency.

    ERIC Educational Resources Information Center

    Winters, Ken

    1990-01-01

    Discusses relevant research findings of clinical assessment of adolescent chemical dependency so that service providers can better address these concerns. Three major issues are discussed: the definition of adolescent chemical dependency, clinical domains of assessment (chemical use problem severity, precipitating and perpetuating risk factors,…

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

    PubMed Central

    Olfson, Emily; Saccone, Nancy L.; Johnson, Eric O.; Chen, Li-Shiun; Culverhouse, Robert; Doheny, Kimberly; Foltz, Steven M.; Fox, Louis; Gogarten, Stephanie M.; Hartz, Sarah; Hetrick, Kurt; Laurie, Cathy C.; Marosy, Beth; Amin, Najaf; Arnett, Donna; Barr, R. Graham; Bartz, Traci M.; Bertelsen, Sarah; Borecki, Ingrid B.; Brown, Michael R.; Chasman, Daniel I.; van Duijn, Cornelia M.; Feitosa, Mary F.; Fox, Ervin R.; Franceschini, Nora; Franco, Oscar H.; Grove, Megan L.; Guo, Xiuqing; Hofman, Albert; Kardia, Sharon L.R.; Morrison, Alanna C.; Musani, Solomon K.; Psaty, Bruce M.; Rao, D.C.; Reiner, Alex P.; Rice, Kenneth; Ridker, Paul M.; Rose, Lynda M.; Schick, Ursula M.; Schwander, Karen; Uitterlinden, Andre G.; Vojinovic, Dina; Wang, Jen-Chyong; Ware, Erin B.; Wilson, Gregory; Yao, Jie; Zhao, Wei; Breslau, Naomi; Hatsukami, Dorothy; Stitzel, Jerry A.; Rice, John; Goate, Alison; Bierut, Laura J.

    2015-01-01

    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 (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 180X 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: OR=1.3, p=3.5×10−11; African ancestry: OR=1.3, p=0.01) and demonstrated that 3 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 risk for smoking-related diseases such as lung cancer. PMID:26239294

  15. 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.

  16. Nicotine vapor inhalation escalates nicotine self-administration.

    PubMed

    Gilpin, Nicholas W; Whitaker, Annie M; Baynes, Brittni; Abdel, Abdelrahim Y; Weil, Madelyn T; George, Olivier

    2014-07-01

    Humans escalate their cigarette smoking over time, and a major obstacle in the field of pre-clinical nicotine addiction research has been the inability to produce escalated nicotine self-administration in rats. In experiment 1, male Wistar rats were trained to respond for nicotine in 2-hour operant sessions, then exposed to chronic intermittent (12 hours/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hours of withdrawal. Rats were tested intermittently on days 1, 3 and 5 of the vapor exposure procedure, then tested with nicotine vapor exposure on 6-15 consecutive days. Rats exhibited transient increases in operant nicotine responding during intermittent testing, regardless of vapor condition, and this responding returned to baseline levels upon resumption of consecutive-days testing (i.e. nicotine deprivation effect). Nicotine vapor-exposed rats then escalated nicotine self-administration relative to both their own baseline (∼200% increase) and non-dependent controls (∼3× higher). In experiment 2, rats were exposed or not exposed to chronic intermittent nicotine vapor, then tested for spontaneous and precipitated somatic signs of nicotine withdrawal. Eight hours following removal from nicotine vapor, rats exhibited robust mecamylamine-precipitated somatic signs of withdrawal. There was a strong correlation between nicotine flow rate and air-nicotine concentration, and the air-nicotine concentrations used in experiments 1 and 2 resemble concentrations experienced by human smokers. Collectively, these results suggest that chronic intermittent nicotine vapor inhalation produces somatic and motivational signs of nicotine dependence, the latter of which is evidenced by escalation of nicotine self-administration.

  17. Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

    PubMed Central

    Kachel, Hamid S.; Patel, Rohit N.; Franzyk, Henrik; Mellor, Ian R.

    2016-01-01

    Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50 = 12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50 values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity. PMID:27901080

  18. Time-dependent changes in nicotine behavioral responsivity during early withdrawal from chronic cocaine administration and attenuation of cocaine sensitization by mecamylamine.

    PubMed

    Szabo, Steven T; Fowler, J C; Froeliger, Brett; Lee, Tong H

    2014-04-01

    Cocaine abuse is associated with a high prevalence of nicotine dependence. In animals, nicotinic antagonists have been reported to block the development of cocaine behavioral sensitization and to attenuate cocaine place preference or self-administration. In the present study, we have determined: (1) changes in the locomotor responses to nicotine challenge during the first week of withdrawal from daily cocaine pretreatment; and (2) effects of the non-selective nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine given during the first 5 days of cocaine withdrawal on the maintenance of cocaine behavioral sensitization. Male Sprague-Dawley rats were pretreated with daily saline (SI) or cocaine (CI) injections for 14 days. In Experiment 1, separate animals in the SI and CI groups received a single nicotine challenge on day 1, 3, or 7 of withdrawal from their respective pretreatments. The CI group displayed enhanced locomotor responses to nicotine as compared to SI controls on days 3 and 7 of withdrawal, but not day 1. In Experiment 2, SI and CI animals were treated once a day with either saline or mecamylamine during the first 5 days of withdrawal, and were subsequently challenged with single cocaine injections on both withdrawal days 7 and 14. Mecamylamine treatment significantly attenuated expression of cocaine behavioral sensitization on both withdrawal days 7 and 14. Time-dependent changes in nicotinic responses occur during the first week of cocaine withdrawal, and intact nAChR neurotransmission during this period may be necessary for maintenance of cocaine behavioral sensitization.

  19. Neuroimaging Insights into the Role of Cortical GABA Systems and the Influence of Nicotine on the Recovery from Alcohol Dependence

    PubMed Central

    Cosgrove, Kelly P.; Esterlis, Irina; Mason, Graeme F.; Bois, Frederic; O'Malley, Stephanie S.; Krystal, John H.

    2011-01-01

    This paper reviews evidence suggesting that nicotine and tobacco smoke profoundly modulate the effects of alcohol on γ-aminobutyric acid (GABA) neuronal function, specifically at the GABAA-benzodiazepine receptor (GABAA-BZR). The focus of this paper is on recent neuroimaging evidence in preclinical models as well as clinical experiments. First, we review findings implicating the role of alcohol at the GABAA-BZR and discuss the changes in GABAA-BZR availability during acute and prolonged alcohol withdrawal. Second, we discuss preclinical evidence that suggests nicotine affects GABA neuronal function indirectly by a primary action at neuronal nicotinic acetylcholine receptors. Third, we show how this evidence converges in studies that examine GABA levels and GABAA-BZRs in alcohol-dependent smokers and nonsmokers, suggesting that tobacco smoking attenuates the chemical changes that occur during alcohol withdrawal. Based on a comprehensive review of literature, we hypothesize that tobacco smoking minimizes the changes in GABA levels that typically occur during the acute cycles of drinking in alcohol-dependent individuals. Thus, during alcohol withdrawal, the continued tobacco smoking decreases the severity of the withdrawal-related changes in GABA chemistry. PMID:21276806

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

    PubMed

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

    2012-01-01

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

  1. Reasons for smoking cessation attempts among Japanese male smokers vary by nicotine dependence level: a cross-sectional study after the 2010 tobacco tax increase

    PubMed Central

    Tanihara, Shinichi; Momose, Yoshito

    2015-01-01

    Objectives To examine the association between smoking cessation attempts during the previous 12 months, motivators to quit smoking and nicotine dependence levels among current male smokers after Japan's massive 2010 tobacco tax increase. Design Cross-sectional study. Setting A self-reported questionnaire about smoking habits, nicotine dependence levels and factors identified as motivators to quit smoking was administered to 9378 employees working at a company located in Fukuoka Prefecture in Japan (as of 1 October 2011). Participants A total of 2251 male current smokers 20–69 years old. Primary and secondary outcome measures Nicotine dependence level assessed by Fagerström Test for Cigarette Dependence (FTCD), smoking cessation attempts during the previous 12 months and motivators for smoking cessation. Results The proportion of current smokers who had attempted to quit smoking within the previous 12 months was 40.6%. Nicotine dependence level of current smokers was negatively associated with cessation attempts during the previous 12 months. Motivators for smoking cessation differed by nicotine dependence levels. ‘The rise in cigarette prices since October 2010’ as a smoking cessation motivator increased significantly at the medium nicotine dependence level (OR 1.44, 95% CI 1.09 to 1.90); however, this association was not statistically significant for individuals with high nicotine dependence (OR 1.24, 95% CI 0.80 to 1.92). ‘Feeling unhealthy’ was significantly negatively associated for medium (OR 0.42, 95% CI 0.27 to 0.65) and high (OR 0.31, 95% CI 0.14 to 0.71) nicotine dependence levels. Trend associations assessed by assigning ordinal numbers to total FTCD score for those two motivators were statistically significant. Conclusions The efficacy of smoking cessation strategies can be improved by considering the target group's nicotine dependence level. For smokers with medium and high nicotine dependence levels, more effective strategies aimed

  2. Nicotine-activated descending facilitation on spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats.

    PubMed

    Pan, Shwu-Fen; Peng, Hsien-Yu; Chen, Chi-Chung; Chen, Mei-Jung; Lee, Shin-Da; Cheng, Chen-Li; Shyu, Jyh-Cherng; Liao, Jiuan-Miaw; Chen, Gin-Den; Lin, Tzer-Bin

    2008-05-01

    This study was conducted to investigate the possible neurotransmitter that activates the descending pathways coming from the dorsolateral pontine tegmentum (DPT) to modulate spinal pelvic-urethra reflex potentiation. External urethra sphincter electromyogram (EUSE) activity in response to test stimulation (TS, 1/30 Hz) and repetitive stimulation (RS, 1 Hz) on the pelvic afferent nerve of 63 anesthetized rats were recorded with or without microinjection of nicotinic cholinergic receptor (nAChR) agonists, ACh and nicotine, to the DPT. TS evoked a baseline reflex activity with a single action potential (1.00 +/- 0.00 spikes/stimulation, n = 40), whereas RS produced a long-lasting reflex potentiation (16.14 +/- 0.96 spikes/stimulation, n = 40) that was abolished by d-2-amino-5-phosphonovaleric acid (1.60 +/- 0.89 spikes/stimulation, n = 40) and was attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (7.10 +/- 0.84 spikes/stimulation, n = 40). ACh and nicotine microinjections to DPT both produced facilitation on the RS-induced reflex potentiation (23.57 +/- 2.23 and 28.29 +/- 2.36 spikes/stimulation, P < 0.01, n = 10 and 20, respectively). Pretreatment of selective nicotinic receptor antagonist, chlorisondamine, reversed the facilitation on RS-induced reflex potentiation caused by nicotine (19.41 +/- 1.21 spikes/stimulation, P < 0.01, n = 10) Intrathecal WAY-100635 and spinal transection at the T(1) level both abolished the facilitation on reflex potentiation resulting from the DPT nicotine injection (12.86 +/- 3.13 and 15.57 +/- 1.72 spikes/stimulation, P < 0.01, n = 10 each). Our findings suggest that activation of nAChR at DPT may modulate N-methyl-d-aspartic acid-dependent reflex potentiation via descending serotonergic neurotransmission. This descending modulation may have physiological/pathological relevance in the neural controls of urethral closure.

  3. Addiction and "Generation Me:" Narcissistic and Prosocial Behaviors of Adolescents with Substance Dependency Disorder in Comparison to Normative Adolescents

    ERIC Educational Resources Information Center

    Carter, Rebecca R.; Johnson, Shannon M.; Exline, Julie J.; Post, Stephen G.; Pagano, Maria E.

    2012-01-01

    The purpose of this study is to explore narcissistic and prosocial behaviors as reported by adolescents with and without substance dependency disorder (SDD). This study employs a quasi-experimental design using SDD adolescents compared with two normative samples of adolescents. In comparison to normative adolescents, adolescents with SDD were…

  4. Neural correlates of craving and resisting craving for tobacco in nicotine dependent smokers.

    PubMed

    Hartwell, Karen J; Johnson, Kevin A; Li, Xingbao; Myrick, Hugh; LeMatty, Todd; George, Mark S; Brady, Kathleen T

    2011-10-01

    Craving is a significant factor which can lead to relapse during smoking quit attempts. Attempts to resist urges to smoke during cue-elicited craving have been shown to activate regions in the brain associated with decision-making, anxiety regulation and visual processing. In this study, 32 treatment-seeking, nicotine-dependent smokers viewed blocks of smoking and neutral cues alternating with rest periods during magnetic resonance imaging scanning in a 3T Siemens scanner (Siemens AG, Erlangen, Bavaria, Germany). While viewing cues or control images, participants were instructed either to 'allow yourself to crave' or 'resist craving.' Data were analyzed with FSL 4.1.5, focused on the smoking cues versus neutral cues contrast, using cluster thresholding (Z > 2.3 and corrected cluster threshold of P = 0.05) at the individual and group levels. During the Crave condition, activation was seen on the left anterior cingulated cortex (LACC), medial prefrontal cortex, left middle cingulate gyrus, bilateral posterior cingulated gyrus and bilateral precuneus, areas associated with attention, decision-making and episodic memory. The LACC and areas of the prefrontal cortex associated with higher executive functioning were activated during the Resist condition. No clear distinctions between group crave and resist analyses as a whole were seen without taking into account specific strategies used to resist the urge to smoke, supporting the idea that craving is associated with some degree of resisting the urge to smoke, and trying to resist is almost always accompanied by some degree of craving. Different strategies for resisting, such as distraction, activated different regions. Understanding the underlying neurobiology of resisting craving to smoke may identify new foci for treatments.

  5. 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

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

    PubMed

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

    2012-01-01

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

  7. 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

  8. Nicotine Lozenges

    MedlinePlus

    ... other nicotine smoking cessation aid, such as the nicotine patch, gum, inhaler, or nasal spray.tell your doctor and pharmacist what other prescription and nonprescription medications, ... non-nicotine smoking cessation aids, such as bupropion (Wellbutrin) or ...

  9. Combined exposure to nicotine and ethanol in adolescent mice: effects on the central cholinergic systems during short and long term withdrawal.

    PubMed

    Ribeiro-Carvalho, A; Lima, C S; Medeiros, A H; Siqueira, N R; Filgueiras, C C; Manhães, A C; Abreu-Villaça, Y

    2009-09-15

    Relapse to drug use is a major public health problem. In this sense, understanding the biological substrates that are affected during withdrawal may provide information to prevent relapse. Both smoking and alcoholic beverage consumption usually begin during adolescence, however, little is known about the basic neurobiology of the combined adolescent exposure, particularly during withdrawal. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChRs), the current study focused on the effects of drug withdrawal on the central cholinergic system. From the 30th to the 45th postnatal day (PN), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We assessed nAChR binding, choline acetyltransferase (ChAT) activity and [(3)H]hemicholinium-3 (HC-3) binding in the cerebral cortex and midbrain of mice at short (PN50) and long term (PN75) withdrawal. NIC and NIC+ETOH promoted nAChR upregulation during a short-term withdrawal. NIC short-term withdrawal elicited an increase in ChAT activity that was reversed by ETOH withdrawal. In addition, NIC+ETOH elicited a decrease in ChAT activity at long term withdrawal. Regarding HC-3, ETOH and NIC+ETOH promoted a decrease that persisted at long-term withdrawal. The present study provides experimental evidence that nicotine and ethanol during adolescence interact resulting in cholinergic system alterations during withdrawal.

  10. Caffeine Use: Association with Nicotine Use, Aggression, and Other Psychopathology in Psychiatric and Pediatric Outpatient Adolescents

    PubMed Central

    Martin, Catherine A.; Cook, Circe; Woodring, John H.; Burkhardt, Gretchen; Guenthner, Greg; Omar, Hatim A.; Kelly, Thomas H.

    2009-01-01

    The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents (average age 14.01 ± 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained from parents and assent from the youth. High caffeine consumption was associated with daily cigarette use; aggressive behavior; conduct, attention deficit/hyperactivity, and social problems; and increased somatic complaints in adolescents. PMID:18516472

  11. Caffeine use: association with nicotine use, aggression, and other psychopathology in psychiatric and pediatric outpatient adolescents.

    PubMed

    Martin, Catherine A; Cook, Circe; Woodring, John H; Burkhardt, Gretchen; Guenthner, Greg; Omar, Hatim A; Kelly, Thomas H

    2008-05-22

    The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents (average age 14.01 +/- 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained from parents and assent from the youth. High caffeine consumption was associated with daily cigarette use; aggressive behavior; conduct, attention deficit/hyperactivity, and social problems; and increased somatic complaints in adolescents.

  12. 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.

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

    PubMed Central

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

    2014-01-01

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

  14. Mimicking maternal smoking and pharmacotherapy of preterm labor: interactions of fetal nicotine and dexamethasone on serotonin and dopamine synaptic function in adolescence and adulthood.

    PubMed

    Slotkin, Theodore A; Seidler, Frederic J

    2010-04-29

    Fetal coexposure to nicotine and dexamethasone is common: maternal smoking increases the incidence of preterm delivery and glucocorticoids are the consensus treatment for prematurity. We gave pregnant rats 3mg/kg/day of nicotine throughout gestation, a regimen that reproduces smokers' plasma levels, and then on gestational days 17, 18 and 19, we administered 0.2mg/kg of dexamethasone. We evaluated developmental indices for serotonin (5HT) and dopamine synaptic function throughout adolescence, young adulthood and later adulthood, assessing the brain regions possessing major 5HT and dopamine projections and cell bodies. Males displayed persistent upregulation of 5HT(1A) and 5HT(2) receptors and the 5HT transporter, with a distinct hierarchy of effects: nicotinenicotine and dexamethasone do not simply produce an initial neuronal injury that persists throughout the lifespan but rather, they alter the developmental trajectory of synaptic function. The fact that the combined treatment produced greater effects for many parameters points to potentially worse neurobehavioral outcomes after pharmacotherapy of preterm labor in the offspring of smokers.

  15. Defining technology dependence in children and adolescents.

    PubMed

    Spratling, Regena

    2015-05-01

    The purpose of this review was to identify current terms and definitions used to identify and describe children and adolescents who require technology. A total of 400 articles published from January 2000 through May 2012 were reviewed; 26 articles met the inclusion criteria. The review included only primary research studies that focused on a child and adolescent sample (birth to 18 years old) who required technology. Current terms and definitions used to describe children and adolescents who require technology include technology and complex care. Technology is a constant in both terminology and definitions, and it differentiates this population from the general population of children with chronic illness and special health care needs. This review highlights the need for better, more detailed descriptions of the population of children and adolescents who require technology in their daily lives.

  16. Ethnic differences in smoking rate, nicotine dependence, and cessation-related variables among adult smokers in Hawaii.

    PubMed

    Herzog, Thaddeus A; Pokhrel, Pallav

    2012-12-01

    This study tests hypotheses concerning ethnic disparities in daily cigarette smoking rates, nicotine dependence, cessation motivation, and knowledge and past use of cessation methods (e.g., counseling) and products (e.g., nicotine patch) in a multiethnic sample of smokers in Hawaii. Previous research has revealed significant differences in smoking prevalence among Native Hawaiians, Filipinos, Japanese, and Caucasians in Hawaii. However, no study has examined differences in dependence and cessation-related knowledge and practices among smokers representing these ethnic groups. Participants were recruited through newspaper advertisement as part of a larger smoking cessation intervention study. Participants (N = 919; M age = 45.6, SD = 12.7; 48 % women) eligible to participate provided self-report data through mail and telephone. Participants included 271 self-identified Native Hawaiians, 63 Filipinos, 316 Caucasians, 145 "East Asians" (e.g., Japanese, Chinese), and 124 "other" (e.g., Hispanic, African-American). Pair-wise comparisons of means, controlling for age, gender, income, education, and marital status, indicated that Native Hawaiian smokers reported significantly higher daily smoking rates and higher levels of nicotine dependence compared to East Asians. Native Hawaiian smokers reported significantly lower motivation to quit smoking than Caucasians. Further, Filipino and Native Hawaiian smokers reported lesser knowledge of cessation methods and products, and less frequent use of these methods and products than Caucasians. The results suggest that Native Hawaiian and Filipino smokers could be underserved with regard to receiving cessation-related advice, and may lack adequate access to smoking cessation products and services. In addition, cessation interventions tailored for Native Hawaiian smokers could benefit from a motivational enhancement component.

  17. 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.

  18. A comparison of the autonomy over tobacco scale and the Fagerström test for nicotine dependence.

    PubMed

    Difranza, Joseph R; Savageau, Judith A; Wellman, Robert J

    2012-07-01

    The autonomy over tobacco scale (AUTOS) is a 12-item theory-based instrument used to measure tobacco dependence in smokers. It provides separate measures of three factors that make smoking cessation more difficult: withdrawal symptoms, psychological dependence, and cue-induced urges to use tobacco. We compared the internal reliability and concurrent validity of the AUTOS to those of the Fagerström test for nicotine dependence (FTND). Adult current smokers (n=422; 62% female; 86.8% white; mean age 33.3 years, SD=13.7; 57% daily smokers) completed an anonymous web-based survey that included the AUTOS, the FTND and 11 smoking-related behavioral measures. Cronbach's α was .94 for the AUTOS and α>.75 for each of the 3 subscales; α=.73 for the FTND. The AUTOS and its subscales correlated with all measures of concurrent validity (r=.70 between AUTOS & FTND). The AUTOS correlated better than the FTND with the Hooked on Nicotine Checklist, the longest period of abstinence, latency to wanting, percentage of time a person smokes because of momentary need, pleasure from smoking, days smoked per month, and concern about deprivation. The measures showed similar correlations with the latencies to craving and needing. The FTND correlated better with the duration of smoking and cigarettes smoked per day. Based on these results and those from prior studies, we conclude that the AUTOS offers researchers a valid and highly reliable, theory-based measure that is more versatile in its applications than the FTND.

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

    PubMed

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

    2014-03-01

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

  20. Effects of Nicotine Administration and Stress on Sensory-Gating Depend on Rat Strain and Sex

    DTIC Science & Technology

    1998-01-01

    variable that may 2 interact with nicotine) in an animal model that included several different genotypes (Le., sex and strain). The present research...important to help explain smoking-stress interactions but this argument is based on limited data CAcri, 1994); and, 3) the available, relevant...groups, crowded (non-stressed) females self- administered more fentanyl (an opioid 100 times more potent that morphine ) than did individually-housed

  1. The effect of nicotine on visuospatial attention in chronic spatial neglect depends upon lesion location.

    PubMed

    Vossel, S; Kukolja, J; Thimm, M; Thiel, C M; Fink, G R

    2010-09-01

    The deficit to reorient attention from ipsilesional to contralesional space is one key feature of the spatial neglect syndrome. As previous studies suggest that reorienting of visuospatial attention is modulated by cholinergic neurotransmission, we investigated whether cholinergic stimulation with nicotine (Nicorette 2 mg, Pharmacia/Pfizer, Helsingborg, Sweden) facilitates attentional reorienting in spatial neglect patients. Nine nonsmoking patients with stable neglect symptoms were investigated in a within-subject cross-over design. We used a location-cueing paradigm and analysed reaction time (RT) differences between validly and invalidly cued, as well as between neutrally cued and uncued targets as a function of hemifield and drug. Moreover, since the nicotine effect is mediated by parietal brain areas in healthy subjects, we tested whether lesion location influences the pharmacological effect. Nicotine speeded RTs in valid and invalid trials nonspecifically, without modulating the validity effect in the location-cueing task in the whole group of patients. Lesion-symptom mapping revealed a relationship between lesion site and the pharmacological effect on reorienting to contralesional space in right parietal and temporal brain regions. We conclude that in patients with chronic spatial neglect the performance in the location-cueing paradigm can be modulated by a cholinergic stimulant provided that the lesion spares right parietal and temporal cortex.

  2. 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

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

    PubMed

    Stanwick, Richard

    2015-03-01

    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.

  4. 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

  5. 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

    2016-06-21

    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

  6. Behavioral modulation of neuronal calcium/calmodulin-dependent protein kinase II activity: differential effects on nicotine-induced spinal and supraspinal antinociception in mice.

    PubMed

    Damaj, M Imad

    2007-10-15

    Recent studies have implicated the involvement of Ca(2+)-dependent mechanisms, in particular calcium/calmodulin-dependent protein kinase II (CaM kinase II) in nicotine-induced antinociception using the tail-flick test. The spinal cord was suggested as a possible site of this involvement. The present study was undertaken to investigate the hypothesis that similar mechanisms exist for nicotine-induced antinociception in the hot-plate test, a response thought to be centrally mediated. In order to assess these mechanisms, i.c.v. administered CaM kinase II inhibitors were evaluated for their effects on antinociception produced by either i.c.v. or s.c. administration of nicotine in both tests. In addition, nicotine's analgesic effects were tested in mice lacking half of their CaM kinase II (CaM kinase II heterozygous) and compare it to their wild-type counterparts. Our results showed that although structurally unrelated CaM kinase II inhibitors blocked nicotine's effects in the tail-flick test in a dose-related manner, they failed to block the hot-plate responses. In addition, the antinociceptive effects of systemic nicotine in the tail-flick but not the hot-plate test were significantly reduced in CaM kinase II heterozygous mice. These observations indicate that in contrast to the tail-flick response, the mechanism of nicotine-induced antinociception in the hot-plate test is not mediated primarily via CaM kinase II-dependent mechanisms at the supraspinal level.

  7. Addiction and "Generation Me:" Narcissistic and Prosocial Behaviors of Adolescents with Substance Dependency Disorder in Comparison to Normative Adolescents.

    PubMed

    Carter, Rebecca R; Johnson, Shannon M; Exline, Julie J; Post, Stephen G; Pagano, Maria E

    2012-01-01

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

  8. Nicotine dependence is associated with depression and childhood trauma in smokers with schizophrenia: results from the FACE-SZ dataset.

    PubMed

    Rey, Romain; D'Amato, Thierry; Boyer, Laurent; Brunel, Lore; Aouizerate, Bruno; Berna, Fabrice; Capdevielle, Delphine; Chereau, Isabelle; Chesnoy-Servanin, Gabrielle; Denizot, Hélène; Dorey, Jean-Michel; Dubertret, Caroline; Dubreucq, Julien; Faget, Catherine; Gabayet, Franck; Lancon, Christophe; Mallet, Jasmina; Misdrahi, David; Passerieux, Christine; Schandrin, Aurélie; Schürhoff, Franck; Urbach, Mathieu; Vidailhet, Pierre; Llorca, Pierre-Michel; Fond, Guillaume

    2017-04-07

    In a perspective of personalized care for smoking cessation, a better clinical characterization of smokers with schizophrenia (SZ) is needed. The objective of this study was to determine the clinical characteristics of SZ smokers with severe nicotine (NIC) dependence. 240 stabilized community-dwelling SZ smokers (mean age = 31.9 years, 80.4% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. Severe NIC dependence was defined by a Fagerstrom questionnaire score ≥ 7. Depression was defined by a Calgary score ≥ 6. Childhood trauma was self-reported by the Childhood Trauma Questionnaire score (CTQ). Ongoing psychotropic treatment was recorded. Severe NIC dependence was identified in 83 subjects (34.6%), depression in 60 (26.3%). 44 (22.3%) subjects were treated by antidepressants. In a multivariate model, severe NIC dependence remained associated with depression (OR = 3.2, p = 0.006), male gender (OR = 4.5, p = 0.009) and more slightly with childhood trauma (OR = 1.03, p = 0.044), independently of socio-demographic characteristics, psychotic symptoms severity, psychotropic treatments and alcohol disorder. NIC dependence was independently and strongly associated with, respectively, depression and male gender in schizophrenia, and only slightly with history of childhood trauma. Based on these results, the care of both nicotine dependence and depression should be evaluated for an effective smoking cessation intervention in schizophrenia.

  9. Nicotine dependence, depression, and gender: characterizing phenotypes based on withdrawal discomfort, response to smoking, and ability to abstain.

    PubMed

    Pomerleau, Ovide F; Pomerleau, Cynthia S; Mehringer, Ann M; Snedecor, Sandy M; Ninowski, Raphaela; Sen, Ananda

    2005-02-01

    Smoking is often viewed as a comprehensive phenotype rather than a complex set of traits involving intermediate phenotypes. To explore this issue in a laboratory setting, we tested 69 smokers stratified on depression, nicotine dependence, and gender. On the third day of an initial withdrawal period, we tested for differences among participants in uncued and cued craving and withdrawal; on the fourth day, we exposed them to a controlled dose of smoke and assessed them for physiological and hedonic effects and reduction of craving and withdrawal. Following resumption of smoking for at least a week, we then tested participants on their ability to abstain for an 11-day interval. During the withdrawal test, high-depressed smokers and men exhibited elevated craving and withdrawal scores overall, whereas no differences emerged for dependence. Cue exposure produced significant increases in craving but not withdrawal. During the smoke-exposure test, men were significantly more likely than women, and high-depressed smokers more likely than low-depressed smokers, to show evidence of experiencing pleasurable "buzzes." High-dependent smokers showed significant increases in diastolic blood pressure, possibly suggestive of greater sensitivity to nicotine. During the quit test, high-dependent smokers had more difficulty abstaining than low-dependent smokers, and women more than men; no differences emerged based on depression. Independently of group membership, inability to abstain was predicted by increased anxiety, depression, and difficulty concentrating in response to cue exposure. These findings provide support for the existence of phenotypes that can be distinguished by withdrawal symptomatology (primarily driven by depression) and ability to remain abstinent (primarily driven by dependence).

  10. Adolescent Rats Differ by Genetic Strain in Response to Nicotine Withdrawal

    DTIC Science & Technology

    2007-11-01

    expressed the feeling of need to smoke, driven by mental and physical cravings . They expressed feelings of emptiness, sensations, shakiness, and...reduces feeding (especially of high calorie sweet foods ) in adult rats (male and female) and in male adolescent rats (Abreu-Villaca et aL, 2003; Faraday...order to tailor the appropriate treatment to the appropriate patients. Withdrawal from tobacco use by humans includes irritability, cigarette craving

  11. 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…

  12. Differential Contributions of Alcohol and Nicotine-Derived Nitrosamine Ketone (NNK) to White Matter Pathology in the Adolescent Rat Brain

    PubMed Central

    Tong, Ming; Yu, Rosa; Silbermann, Elizabeth; Zabala, Valerie; Deochand, Chetram; de la Monte, Suzanne M.

    2015-01-01

    Aim Epidemiologic studies have demonstrated high rates of smoking among alcoholics, and neuroimaging studies have detected white matter atrophy and degeneration in both smokers and individuals with alcohol-related brain disease (ARBD). These findings suggest that tobacco smoke exposure may be a co-factor in ARBD. The present study examines the differential and additive effects of tobacco-specific nitrosamine (NNK) and ethanol exposures on the structural and functional integrity of white matter in an experimental model. Methods Adolescent Long Evans rats were fed liquid diets containing 0 or 26% ethanol for 8 weeks. In weeks 3–8, rats were treated with nicotine-derived nitrosamine ketone (NNK) (2 mg/kg, 3×/week) or saline by i.p. injection. In weeks 7–8, the ethanol group was binge-administered ethanol (2 g/kg; 3×/week). Results Ethanol, NNK and ethanol + NNK caused striking degenerative abnormalities in white matter myelin and axons, with accompanying reductions in myelin-associated glycoprotein expression. Quantitative RT-PCR targeted array and heatmap analyses demonstrated that ethanol modestly increased, whereas ethanol + NNK sharply increased expression of immature and mature oligodendroglial genes, and that NNK increased immature but inhibited mature oligodendroglial genes. In addition, NNK modulated expression of neuroglial genes in favor of growth cone collapse and synaptic disconnection. Ethanol- and NNK-associated increases in FOXO1, FOXO4 and NKX2-2 transcription factor gene expression could reflect compensatory responses to brain insulin resistance in this model. Conclusion Alcohol and tobacco exposures promote ARBD by impairing myelin synthesis, maturation and integrity via distinct but overlapping mechanisms. Public health measures to reduce ARBD should target both alcohol and tobacco abuses. PMID:26373813

  13. Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated nicotine content.

    PubMed

    Richter, Patricia; Spierto, Francis W

    2003-12-01

    Smokeless tobacco is a complex chemical mixture, including not only the components of the tobacco leaf but also chemicals added during the manufacturing process. Smokeless tobacco contains the addictive chemical nicotine and more than 20 cancer-causing chemicals, including the potent tobacco-specific nitrosamines. The National Toxicology Program of the National Institutes of Health has concluded that oral use of smokeless tobacco is a human carcinogen. Therefore, smokeless tobacco is not a safe alternative to cigarettes. In fact, smokeless tobacco use begins primarily during early adolescence and can lead to nicotine dependence and increased risk of becoming a cigarette smoker. Under the Comprehensive Smokeless Tobacco Health Education Act of 1986 (15 U.S.C. 4401 et seq., Pub. L. 99-252), tobacco manufacturers report annually to the Centers for Disease Control and Prevention (CDC) on the total nicotine, unprotonated nicotine, pH, and moisture content of their smokeless tobacco products. This information is considered "trade secret," or confidential, in accordance with 5 U.S.C. 552(b)(4) and 18 U.S.C. 1905 and cannot be released to the public. In an effort to provide consumers and researchers with information on the nicotine content of smokeless tobacco, CDC arranged for the analysis of popular brands of smokeless tobacco. The results of this CDC study show that pH is a primary factor in the amount of nicotine that is in the most readily absorbable, unprotonated form. Furthermore, this study found that the brands of moist snuff smokeless tobacco with the largest amount of unprotonated nicotine also are the most frequently sold brands.

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

    PubMed Central

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

    2013-01-01

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

  15. cAMP-dependent protein kinase inhibits α7 nicotinic receptor activity in layer 1 cortical interneurons through activation of D1/D5 dopamine receptors

    PubMed Central

    Komal, Pragya; Estakhr, Jasem; Kamran, Melad; Renda, Anthony; Nashmi, Raad

    2015-01-01

    Phosphorylation of ion channels, including nicotinic acetylcholine receptors (nAChRs), by protein kinases plays a key role in the modification of synaptic transmission and neuronal excitability. α7 nAChRs are the second most prevalent nAChR subtype in the CNS following α4β2. Serine 365 in the M3–M4 cytoplasmic loop of the α7 nAChR is a phosphorylation site for protein kinase A (PKA). D1/D5 dopamine receptors signal through the adenylate cyclase–PKA pathway and play a key role in working memory and attention in the prefrontal cortex. Thus, we examined whether the dopaminergic system, mediated through PKA, functionally interacts with the α7-dependent cholinergic neurotransmission. In layer 1 interneurons of mouse prefrontal cortex, α7 nicotinic currents were decreased upon stimulation with 8-Br-cAMP, a PKA activator. In HEK 293T cells, dominant negative PKA abolished 8-Br-cAMP's effect of diminishing α7 nicotinic currents, while a constitutively active PKA catalytic subunit decreased α7 currents. In brain slices, the PKA inhibitor KT-5720 nullified 8-Br-cAMP's effect of attenuating α7 nicotinic responses, while applying a PKA catalytic subunit in the pipette solution decreased α7 currents. 8-Br-cAMP stimulation reduced surface expression of α7 nAChRs, but there was no change in single-channel conductance. The D1/D5 dopamine receptor agonist SKF 83822 similarly attenuated α7 nicotinic currents from layer 1 interneurons and this attenuation of nicotinic current was prevented by KT-5720. These results demonstrate that dopamine receptor-mediated activation of PKA negatively modulates nicotinic neurotransmission in prefrontal cortical interneurons, which may be a contributing mechanism of dopamine modulation of cognitive behaviours such as attention or working memory. PMID:25990637

  16. [Care structures for drug dependent children and adolescents].

    PubMed

    Thoms, E; Oehme, M

    2003-12-01

    Children and adolescents abusing drugs present a special challenge for our health system. Special risks for the development of drug dependence are psychic diseases of parents, familial addiction or multiply burdened families. The treatment of drug-addicted children and adolescents in child and youth psychiatry requires a highly individualised therapy programme as well as a pedagogic and therapeutic setting corresponding to age. 745 patients were examined in a retrospective study between 1998 and 2001. The results are shown below. 68% of the patients had a relevant psychiatric second diagnosis, 39 Patients of the examined drug addicted children and adolescents were diagnosed with an additional psychotic disturbance. A study of children and youth psychiatry clinics in the fall of 2001 showed that sufficient clinical care for drug-addicted children and adolescents is still lacking.

  17. Assessment of the correlations between nicotine dependence, exhaled carbon monoxide levels and oral hygiene status: an observational study

    PubMed Central

    MOGA, MINODORA; BOSCA, ADINA BIANCA; BONDOR, COSMINA IOANA; ILEA, ARANKA; LUCACIU, ONDINE PATRICIA; IONEL, ANCA; MAN, MILENA ADINA; RAJNOVEANU, RUXANDRA MIOARA; CÂMPIAN, RADU SEPTIMIU

    2017-01-01

    Background and aim Cigarette smoking has negative effects on general health, including oral health. The aim of our study was to assess the correlations between nicotine dependence, exhaled carbon monoxide levels and oral hygiene status. Methods Smoker and non-smoker participants were enrolled in this observational study. The Fagerström test was used to classify nicotine dependences: low (score: 0–3), medium (score: 4–6) or high (score: 7–10). The oral hygiene status was classified according to the oral hygiene indices of plaque, calculus and gingival inflammation. Lastly, the exhaled carbon monoxide levels were measured with a MicroSmokelyzer (Bedfont Scientific Ltd., Kent, United Kingdom). Results Sixty five participants (50 smokers in the study group and 15 non-smokers in the control group) were enrolled between 11th and 29th of January 2016. No statistical differences were observed between the study group and the control group in terms of age (mean age±SD 23.5±1.9 and 24.0±1.5, respectively) or gender (50% and 26.6%, respectively). A statistically significant difference was observed between the 2 groups in terms of plaque, (p=0.036), calculus (p=0.001) and gingival indices (p<0.001). A positive correlation was found between the exhaled levels of carbon monoxide and the general Fagerström score (r=0.97, p<0.001) or the Fagerström score in smokers (r=0.93, p<0.001); a negative correlation was observed between the exhaled carbon monoxide levels and the number of tooth brushings daily (r=−0.41, p=0.001). The plaque index was statistically significantly associated with the exhaled carbon monoxide levels (p=0.008), general Fagerström score (p=0.016) and number of tooth brushings daily (p<0.001). The calculus and gingival indices were statistically significantly associated with the exhaled carbon monoxide levels (p<0.001), general Fagerström score (p<0.001) and score in smoker participants (p=0.029 and p=0.001, respectively) as well as the number of

  18. 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

  19. Activation of nicotinic acetylcholine receptors enhances a slow calcium-dependent potassium conductance and reduces the firing of stratum oriens interneurons.

    PubMed

    Griguoli, Marilena; Scuri, Rossana; Ragozzino, Davide; Cherubini, Enrico

    2009-09-01

    A large variety of distinct locally connected GABAergic cells are present in the hippocampus. By releasing GABA into principal cells and interneurons, they exert a powerful control on neuronal excitability and are responsible for network oscillations crucial for information processing in the brain. Here, whole-cell patch clamp recordings in current and voltage clamp mode were used to study the functional role of nicotinic acetylcholine receptors (nAChRs) on the firing properties of stratum oriens interneurons in hippocampal slices from transgenic mice expressing enhanced green fluorescent protein in a subpopulation of GABAergic cells containing somatostatin (GIN mice). Unexpectedly, activation of nAChRs by nicotine or endogenously released acetylcholine strongly enhanced spike frequency adaptation. This effect was blocked by apamin, suggesting the involvement of small calcium-dependent potassium channels (SK channels). Nicotine-induced reduction in firing frequency was dependent on intracellular calcium rise through calcium-permeable nAChRs and voltage-dependent calcium channels activated by the depolarizing action of nicotine. Calcium imaging experiments directly showed that nicotine effects on firing rate were correlated with large increases in intracellular calcium. Furthermore, blocking ryanodine receptors with ryanodine or sarcoplasmic-endoplasmic reticulum calcium ATPase with thapsygargin or cyclopiazonic acid fully prevented the effects of nicotine, suggesting that mobilization of calcium from the internal stores contributed to the observed effects. By regulating cell firing, cholinergic signalling through nAChRs would be instrumental for fine-tuning the output of stratum oriens interneurons and correlated activity at the network level.

  20. 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

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

    PubMed

    Hughes, John R

    2011-09-01

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

  2. Nicotinic receptors, memory, and hippocampus.

    PubMed

    Kutlu, Munir Gunes; Gould, Thomas J

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) modulate the neurobiological processes underlying hippocampal learning and memory. In addition, nicotine's ability to desensitize and upregulate certain nAChRs may alter hippocampus-dependent memory processes. Numerous studies have examined the effects of nicotine on hippocampus-dependent learning, as well as the roles of low- and high-affinity nAChRs in mediating nicotine's effects on hippocampus-dependent learning and memory. These studies suggested that while acute nicotine generally acts as a cognitive enhancer for hippocampus-dependent learning, withdrawal from chronic nicotine results in deficits in hippocampus-dependent memory. Furthermore, these studies demonstrated that low- and high-affinity nAChRs functionally differ in their involvement in nicotine's effects on hippocampus-dependent learning. In the present chapter, we reviewed studies using systemic or local injections of acute or chronic nicotine, nAChR subunit agonists or antagonists; genetically modified mice; and molecular biological techniques to characterize the effects of nicotine on hippocampus-dependent learning.

  3. 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

  4. Alcohol and nicotine administration inhibits serotonin synthesis and tryptophan hydroxylase expression in dorsal and median raphe of young rats.

    PubMed

    Jang, Mi-Hyeon; Shin, Min-Chul; Lee, Taeck-Hyun; Kim, Young-Pyo; Jung, Sae-Bin; Shin, Dong-Hoon; Kim, Hong; Kim, Sung-Soo; Kim, Ee-Hwa; Kim, Chang-Ju

    2002-08-30

    Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of various neuropsychiatric disorders. In the present study, the effects of alcohol and nicotine on the synthesis of 5-HT and the expression of tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT synthesis, in the dorsal and median raphe of young rats were investigated via immunohistochemistry. The numbers of the 5-HT-positive and TPH-positive cells were reduced by alcohol and nicotine treatment in a dose-dependent manner. Based on the results, it can be suggested that the pathogenesis of alcohol- and nicotine-induced neuropsychological disorders involves alcohol- and nicotine-induced suppression of 5-HT synthesis and TPH expression in raphe, and that this may be of particular relevance in the consumption of alcohol and nicotine during adolescence.

  5. Individual differences in oral nicotine intake in rats.

    PubMed

    Nesil, Tanseli; Kanit, Lutfiye; Collins, Allan C; Pogun, Sakire

    2011-01-01

    To study individual differences in nicotine preference and intake, male and female rats were given free access to a choice of oral nicotine (10 or 20 mg/L) or water for 24 h/day for periods of at least six weeks, starting at adolescence or adulthood. A total of 341 rats, were used in four different experiments; weight, nicotine intake and total liquid consumption were recorded weekly. Results show that rats can discriminate nicotine from water, can regulate their intake, and that there are readily detected individual differences in nicotine preference. Ward analyses indicated that the animals could be divided into minimum, median and maximum preferring subgroups in all experiments. The effect of saccharine on nicotine intake was also evaluated; although the addition of saccharine increased total intake, rats drank unsweetened nicotine solutions and those with higher preferences for nicotine, preferred nicotine over water with or without saccharine added. Nicotine reduced weight gain and the effect was more pronounced in females than males. The average nicotine consumption of adolescent rats was higher than adults and nicotine exposure during adolescence reduced nicotine intake in adult rats. About half of the rats which had access to nicotine as adolescents and also as adults had a persistent pattern of consumption; the behavior was very stable in the female minimum preferring groups and a much higher ratio of rats sustained their adolescent behavior as adults. The change in preference was more pronounced when there was an interval between adolescent and adult exposure; female rats showed a more stable behavior than males suggesting a greater role for environmental influences on males. In conclusion, marked individual differences were observed in oral nicotine intake as measured in a continuous access 2-bottle choice test. Age and sex of the subjects and previous exposure to nicotine are significant factors which affect preference in rats.

  6. Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeutics

    PubMed Central

    Benowitz, Neal L.

    2010-01-01

    Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized byCYP2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist. PMID:18834313

  7. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.

    PubMed

    Benowitz, Neal L

    2009-01-01

    Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized by CYP 2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.

  8. Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence.

    PubMed

    McClain, Justin A; Morris, Stephanie A; Marshall, S Alexander; Nixon, Kimberly

    2014-07-01

    The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence. Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence. Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively. The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence. Although these results mirror the magnitude of reactive neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults. The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats. Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.

  9. Menthol facilitates the intravenous self-administration of nicotine in rats

    PubMed Central

    Wang, Tengfei; Wang, Bin; Chen, Hao

    2014-01-01

    Menthol is preferred by ~25% of smokers and is the most common flavoring additive in tobacco and electronic cigarettes. Although some clinical studies have suggested that menthol facilitates the initiation of smoking and enhances the dependence on nicotine, many controversies remain. Using licking as the operant behavior, we found that adolescent rats self-administering nicotine (30μg/kg/infusion, free base, i.v.) with contingent oral menthol (60μl, 0.01% w/v) obtained significantly more infusions than rats receiving a vehicle cue or rats self-administering i.v. saline with a menthol cue. Rats yoked to their menthol-nicotine masters emitted significantly fewer licks on the active spouts, indicating that contingent pairing between nicotine and menthol is required for sustained nicotine intake. Rats that self-administered nicotine with a menthol cue also exhibited a long-lasting extinction burst and robust reinstatement behavior, neither of which were observed in rats that self-administered saline with a menthol cue. The cooling sensation of menthol is induced by activating the transient receptor potential M8 (TRPM8) channel. When WS-23, an odorless agonist of the TRPM8 channel, was used as a contingent cue for nicotine, the rats obtained a similar number of nicotine infusions as the rats that were provided a menthol cue and exhibited a strong preference for the active spout. In contrast, highly appetitive taste and odor cues failed to support nicotine self-administration. These data indicated that menthol, likely by inducing a cooling sensation, becomes a potent conditioned reinforcer when it is contingently delivered with nicotine. Together, these results provide a key behavioral mechanism by which menthol promotes the use of tobacco products or electronic cigarettes. PMID:25566005

  10. 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…

  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. Impact and duration of brief surgeon-delivered smoking cessation advice on attitudes regarding nicotine dependence and tobacco harms for patients with peripheral arterial disease

    PubMed Central

    Newhall, Karina; Suckow, Bjoern; Spangler, Emily; Brooke, Benjamin S.; Schanzer, Andres; Tan, TzeWoei; Burnette, Mary; Edelen, Maria Orlando; Farber, Alik; Goodney, Philip

    2016-01-01

    Background Despite the recognized benefits of smoking cessation, many clinicians question if a brief smoking cessation intervention can help dedicated smokers with peripheral arterial disease understand nicotine dependence and harms related to smoking. We investigated the impact and durability of a multi-modal smoking cessation intervention on patient attitudes regarding nicotine dependence and the health effects of smoking. Methods We conducted a pilot cluster randomized trial of a brief smoking cessation intervention at eight vascular surgery practices between September 1, 2014 and August 31, 2015. Compared with control sites, patients at intervention sites received protocolized brief cessation counseling, medications and referrals to a quitline. After their clinic visit and again at 3 months, participants completed a brief survey about patient attitudes regarding nicotine dependence and the health effects of smoking. Responses to questions were analyzed using Chi2 and student’s t-tests. Results All trial participants (n=156) complete the initial survey, and 75 (45%) participants completed the follow-up survey. Intervention and control patients both reported a greater than 30-pack-year history (80% vs 90%, p=0.07) and previous failed quit attempts (77% vs 78%, p=0.8). Compared to usual care, patients in the intervention group were more likely to describe hearing advice to quit from their surgeon (98% vs. 77%, p<0.001), and expressed “a lot” or “some” interest in quitting (95.4% vs 85.7%, p=0.05). Patients in the intervention group were also more likely to acknowledge their addictive behaviors, consistently scoring higher on question bank items regarding nicotine addiction (52.9 vs 48.0, p=0.006) and the negative health effects of smoking (scaled score 56.6 vs 50.6, p=0.001). When re-surveyed three months after intervention, patients in the intervention group had larger declines in nicotine dependence and health effects domains, suggesting durable impact

  13. The frequency of early-activated hapten-specific B cell subsets predicts the efficacy of vaccines for nicotine dependence

    PubMed Central

    Laudenbach, M; Tucker, AM; Runyon, SP; Carroll, FI; Pravetoni, M

    2015-01-01

    Therapeutic vaccines for nicotine addiction show pre-clinical efficacy. Yet, clinical evaluation of the first-generation nicotine vaccines did not meet expectations because only a subset of immunized subjects achieved effective serum antibody levels. Recent studies suggest that vaccine design affects B cell activation, and that the frequency of the hapten-specific B cell subsets contributes to vaccine efficacy against drugs of abuse. To extend this hypothesis to nicotine immunogens, we synthesized a novel hapten containing a carboxymethylureido group at the 2-position of the nicotine structure (2CMUNic) and compared its efficacy to the previously characterized 6CMUNic hapten. Haptens were conjugated to the keyhole limpet hemocyanin (KLH) carrier protein, and evaluated for efficacy against nicotine in mice using the clinically approved alum adjuvant. Using a novel fluorescent antigen-based magnetic enrichment strategy paired with multicolor flow cytometry analysis, polyclonal hapten-specific B cell subsets were measured in mice immunized with either 6CMUNic-KLH or 2CMUNic-KLH. The 6CMUNic-KLH showed significantly greater efficacy than 2CMUNic-KLH on nicotine distribution to serum and to the brain. The 6CMUNic-KLH elicited higher anti-nicotine serum antibody titers, and a greater frequency of hapten-specific B cells than 2CMUNic-KLH. Within the splenic polyclonal B cell population, a higher number of hapten-specific IgMhigh and germinal center B cells predicted greater vaccine efficacy against nicotine distribution. These early pre-clinical findings suggest that hapten structure affects activation of B cells, and that variations in the frequency of early-activated hapten-specific B cell subsets underlie individual differences in vaccine efficacy. PMID:26409811

  14. Pre-clinical properties of the α4β2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence

    PubMed Central

    Rollema, H; Shrikhande, A; Ward, KM; Tingley, FD; Coe, JW; O'Neill, BT; Tseng, E; Wang, EQ; Mather, RJ; Hurst, RS; Williams, KE; de Vries, M; Cremers, T; Bertrand, S; Bertrand, D

    2010-01-01

    Background and purpose: Smoking cessation trials with three high-affinity partial agonists of α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human α4β2 nAChRs. Experimental approach: Rat plasma and brain pharmacokinetics were characterized and used to predict human steady-state plasma and brain concentrations following recommended doses of each of the three compounds. The pharmacological characterization included in vitro affinities at different nAChR subtypes, functional efficacies and potencies at the human α4β2 nAChR, as well as in vivo effects on rat mesolimbic dopamine turn-over. Key results: A comparison of predicted human brain concentrations following therapeutic doses demonstrated that varenicline and nicotine, but not dianicline and cytisine, can extensively desensitize and, to a lesser extent, activate α4β2 nAChRs. The limited clinical efficacy of dianicline may be accounted for by a combination of weak functional potency at α4β2 nAChRs and moderate brain penetration, while recommended doses of cytisine, despite its high in vitro potency, are predicted to result in brain concentrations that are insufficient to affect α4β2 nAChRs. Conclusions and implications: The data provide a plausible explanation for the higher abstinence rate in smoking cessation trials following treatment with varenicline than with the two other α4β2 nAChR partial agonists. In addition, this retrospective analysis demonstrates the usefulness of combining in vitro and in vivo parameters with estimated therapeutic human brain concentrations for translation to clinical efficacy. PMID:20331614

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

    PubMed Central

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

    2015-01-01

    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 multi-sensory, 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

  16. 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.

  17. The neuroeconomics of nicotine dependence: A preliminary study of delay discounting of monetary and cigarette rewards in smokers using fMRI

    PubMed Central

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

    2012-01-01

    Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence. PMID:22633679

  18. 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.

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

    PubMed

    O'Dell, Laura E; Torres, Oscar V

    2014-01-01

    Women are particularly more vulnerable to tobacco use than men. This review proposes a unifying hypothesis that females experience greater rewarding effects of nicotine and more intense stress produced by withdrawal than males. We also provide a neural framework whereby estrogen promotes greater rewarding effects of nicotine in females via enhanced dopamine release in the nucleus accumbens (NAcc). During withdrawal, we suggest that corticotropin-releasing factor (CRF) stress systems are sensitized and promote a greater suppression of dopamine release in the NAcc of females versus males. Taken together, females display enhanced nicotine reward via estrogen and amplified effects of withdrawal via stress systems. Although this framework focuses on sex differences in adult rats, it is also applied to adolescent females who display enhanced rewarding effects of nicotine, but reduced effects of withdrawal from this drug. Since females experience strong rewarding effects of nicotine, a clinical implication of our hypothesis is that specific strategies to prevent smoking initiation among females are critical. Also, anxiolytic medications may be more effective in females that experience intense stress during withdrawal. Furthermore, medications that target withdrawal should not be applied in a unilateral manner across age and sex, given that nicotine withdrawal is lower during adolescence. This review highlights key factors that promote nicotine use in females, and future studies on sex-dependent interactions of stress and reward systems are needed to test our mechanistic hypotheses. Future studies in this area will have important translational value toward reducing health disparities produced by nicotine use in females. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  20. 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

  1. Electronic cigarettes and nicotine clinical pharmacology

    PubMed Central

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  2. Baseline impulsive choice predicts the effects of nicotine and nicotine withdrawal on impulsivity in rats.

    PubMed

    Kayir, Hakan; Semenova, Svetlana; Markou, Athina

    2014-01-03

    Impulsive choice, a form of impulsivity, is associated with tobacco smoking in humans. Trait impulsivity may be a vulnerability factor for smoking, or smoking may lead to impulsive behaviors. We investigated the effects of 14-day nicotine exposure (6.32mg/kg/day base, subcutaneous minipumps) and spontaneous nicotine withdrawal on impulsive choice in low impulsive (LI) and high impulsive (HI) rats. Impulsive choice was measured in the delayed reward task in which rats choose between a small immediate reward and a large delayed reward. HI and LI rats were selected from the highest and lowest quartiles of the group before exposure to nicotine. In non-selected rats, nicotine or nicotine withdrawal had no effect on impulsive choice. In LI rats, chronic nicotine exposure decreased preference for the large reward with larger effects at longer delays, indicating increased impulsive choice. Impulsive choices for the smaller immediate rewards continued to increase during nicotine withdrawal in LI rats. In HI rats, nicotine exposure and nicotine withdrawal had no effect on impulsive choice, although there was a tendency for decreased preference for the large reward at short delays. These results indicate that nicotine- and nicotine withdrawal-induced increases in impulsive choice depend on trait impulsivity with more pronounced increases in impulsive choice in LI compared to HI subjects. Increased impulsivity during nicotine exposure may strengthen the addictive properties of nicotine and contribute to compulsive nicotine use.

  3. 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…

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

    PubMed Central

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

    2012-01-01

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

  5. d-Cycloserine administration does not affect neurocognition in concurrent cocaine- and nicotine-dependent volunteers.

    PubMed

    Kalechstein, A D; Yoon, J H; Mahoney, J J; Newton, T F; Chang, L; De La Garza, R

    2012-12-01

    Neurocognitive impairment is a well-documented consequence of long-term, repeated cocaine exposure and has been identified as an important target of treatment. Thus, this study sought to determine whether the N-methyl-d-aspartate (NMDA) partial agonist, d-cycloserine could improve neurocognitive performance in a sample of 27 long-term, high dose cocaine dependent individuals who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a single dose of 0 or 50mg of d-cycloserine would enhance performance on measures of attention/information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that d-cycloserine did not modulate neurocognition in this cohort, though there are a number of factors that may have mitigated the effects of d-cycloserine in this particular study. The negative findings notwithstanding, the current study serves as a springboard for future investigations that will examine whether other medications that can modulate neurocognition in cocaine-dependent study participants.

  6. [Smoking prevalence, nicotine dependence and effects of low cost cigarette sale among military healthcare personal in Turkish Republic of Northern Cyprus].

    PubMed

    Günay, Ersin; Simşek, Ziya; Kutucularoğlu, Gürkan; Metinyurt, Gürkan

    2010-01-01

    Health professionals, particularly clinicians and nurses in the community have an important role in preventing to start smoking. In our study; we aimed to determine the prevalence of cigarette smoking, nicotine dependence level and the effects of low price tobacco sale among healthcare personal in a military hospital. A questionnaire was applied to healthcare personal, which evaluates their smoking habits, nicotine dependence level with Fagerström Test for Nicotine Dependence (FTND) and the effects of low cost cigarette sale on smoking habits. Seventy male and 46 female among 138 healthcare personals (84%) responded to the questionnaire. Mean age of participants was 33.7 ± 5.6. Among all participants, 53.4% were smoking. There was no significant difference between male and female participants in case of smoking prevalence (p> 0.05). Seven participants who started smoking regularly after they appointed to Turkish Republic of Northern Cyprus explained why they started smoking as secondary to lower cigarette prices in this country. 48.3% of participants (40% of male smokers and 59.3% of female smokers) reported increased cigarette consumption as a result of low cost cigarette sales. There was a significant difference between male and female participants in case of increase in cigarette consumption (< 0.05). According to results of FTND, about 70% of participants were low and very low-dependant, and about 22% were high and very high- dependant smokers. Smoking prevalence of healthcare personal who participated in our study was higher than that reported for community and for other healthcare personal.

  7. 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

  8. 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 ...

  9. Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine Gum

    PubMed Central

    Digard, Helena; Proctor, Christopher; Kulasekaran, Anuradha; Malmqvist, Ulf

    2013-01-01

    Introduction: Snus is a smokeless tobacco product traditionally used in Scandinavia and available in pouched or loose forms. The objective of this study was to determine nicotine absorption for current pouched and loose snus products in comparison with a cigarette and an over-the-counter nicotine gum. Methods: We conducted an open-label, randomized, 6-way, crossover study involving 20 healthy snus and cigarette users. One of 6 products (2 pouched snus, 2 weights of loose snus, a cigarette, and a nicotine gum) was administered at each of 6 visits. Blood samples were taken at intervals over 120 min and sensory perception assessed by questionnaire. Results: For the 4 smokeless tobacco products and the nicotine gum, blood plasma levels of nicotine were ranked according to total nicotine content as follows: loose snus (27.1 mg nicotine) > pouched snus (14.7 mg nicotine) > loose snus (10.8 mg nicotine) = pouched snus (10.7 mg nicotine) > nicotine gum (4.2 mg nicotine). The area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) of nicotine ranged from 26.9 to 13.1 ng.h/ml and 17.9 to 9.1 ng.h/ml, respectively across all the products. Nicotine was absorbed more rapidly from the cigarette but systemic exposure was within the range of the smokeless tobacco products (AUC = 14.8 ng.h/ml; Cmax = 12.8 ng.h/ml). Conclusions: This study has generated new information on comparative nicotine absorption from a cigarette, loose snus, and pouched snus typical of products sold in Scandinavia. The similar nicotine absorption for 1 g portions of loose and pouched snus with approximately 11 mg of nicotine indicate that absorption kinetics were dependent on quantity of tobacco by weight and total nicotine content rather than product form. PMID:22585541

  10. Objective and subjective memory ratings in cannabis-dependent adolescents

    PubMed Central

    McClure, Erin A.; Lydiard, Jessica B.; Goddard, Scott D.; Gray, Kevin M.

    2015-01-01

    Background and Objectives Cannabis is the most widely used illicit substance worldwide, with an estimated 160 million users. Among adolescents, rates of cannabis use are increasing, while the perception of detrimental effects of cannabis use is declining. Difficulty with memory is one of the most frequently noted cognitive deficits associated with cannabis use, but little data exists exploring how well users can identify their own memory deficits, if present. Methods The current secondary analysis sought to characterize objective verbal and visual memory performance via a neurocognitive battery in cannabis-dependent adolescents enrolled in a pharmacotherapeutic cannabis cessation clinical trial (N=112) and compare this to a single self-reported item assessing difficulties with memory loss. Exploratory analyses also assessed dose-dependent effects of cannabis on memory performance. Results A small portion of the study sample (10%) endorsed a “serious problem” with memory loss. Those participants reporting “no problem” or “serious problem” scored similarly on visual and verbal memory tasks on the neurocognitive battery. Exploratory analyses suggested a potential relationship between days of cannabis use, amount of cannabis used, and gender with memory performance. Conclusions and Scientific Significance This preliminary and exploratory analysis suggests that a sub-set of cannabis users may not accurately perceive difficulties with memory. Further work should test this hypothesis with the use of a control group, comprehensive self-reports of memory problems, and adult populations that may have more years of cannabis use and more severe cognitive deficits. PMID:25823635

  11. 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…

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

    PubMed

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

    2013-04-01

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

  13. 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

  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. Differential Contributions of Alcohol and the Nicotine-Derived Nitrosamine Ketone (NNK) to Insulin and Insulin-Like Growth Factor Resistance in the Adolescent Rat Brain

    PubMed Central

    Tong, Ming; Yu, Rosa; Deochand, Chetram; de la Monte, Suzanne M.

    2015-01-01

    Aims Since epidemiologic studies suggest that tobacco smoke toxins, e.g. the nicotine-derived nitrosamine ketone (NNK) tobacco-specific nitrosamine, can be a co-factor in alcohol-related brain disease (ARBD), we examined the independent and additive effects of alcohol and NNK exposures on spatial learning/memory, and brain insulin/IGF signaling, neuronal function and oxidative stress. Methods Adolescent Long Evans rats were fed liquid diets containing 0 or 26% caloric ethanol for 8 weeks. During weeks 3–8, rats were treated with i.p. NNK (2 mg/kg, 3×/week) or saline. In weeks 7–8, ethanol groups were binge-administered ethanol (2 g/kg; 3×/week). In week 8, at 12 weeks of age, rats were subjected to Morris Water Maze tests. Temporal lobes were used to assess molecular indices of insulin/IGF resistance, oxidative stress and neuronal function. Results Ethanol and NNK impaired spatial learning, and NNK ± ethanol impaired memory. Linear trend analysis demonstrated worsening performance from control to ethanol, to NNK, and then ethanol + NNK. Ethanol ± NNK, caused brain atrophy, inhibited insulin signaling through the insulin receptor and Akt, activated GSK-3β, increased protein carbonyl and 3-nitrotyrosine, and reduced acetylcholinesterase. NNK increased NTyr. Ethanol + NNK had synergistic stimulatory effects on 8-iso-PGF-2α, inhibitory effects on p-p70S6K, tau and p-tau and trend effects on insulin-like growth factor type 1 (IGF-1) receptor expression and phosphorylation. Conclusions Ethanol, NNK and combined ethanol + NNK exposures that begin in adolescence impair spatial learning and memory in young adults. The ethanol and/or NNK exposures differentially impair insulin/IGF signaling through neuronal growth, survival and plasticity pathways, increase cellular injury and oxidative stress and reduce expression of critical proteins needed for neuronal function. PMID:26373814

  16. Chronic low-grade peripheral inflammation is associated with severe nicotine dependence in schizophrenia: results from the national multicentric FACE-SZ cohort.

    PubMed

    Fond, G; Berna, F; Andrianarisoa, M; Godin, O; Leboyer, M; Brunel, L; Aouizerate, B; Capdevielle, D; Chereau, I; D'Amato, T; Denizot, H; Dubertret, C; Dubreucq, J; Faget, C; Gabayet, F; Llorca, P M; Mallet, J; Misdrahi, D; Passerieux, C; Richieri, R; Rey, R; Schandrin, A; Urbach, M; Vidailhet, P; Boyer, L; Schürhoff, F

    2017-02-25

    Chronic peripheral inflammation (CPI) has been associated with cognitive impairment in schizophrenia (SZ). However, its sources remain unclear, more specifically it is not known whether tobacco smoking is a source of inflammation or not in SZ subjects. Moreover, nicotine (NIC), the major psychoactive compound of tobacco, shows strong anti-inflammatory properties in vitro, as well as inducing a severe biological dependence when administered repeatedly. The objective of the present study was to determine if CPI was associated with tobacco smoking and/or NIC dependence in schizophrenia. Three hundred and forty five stabilized community-dwelling SZ subjects aged 16 years or older (mean age = 32 years, 73% male) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. CPI was defined by a highly sensitive C-reactive protein (hsCRP) ≥3 mg/L. Current tobacco status was self-declared. Severe NIC dependence was defined by a Fagerstrom Test for Nicotine Dependence score ≥7. Overall, 159 (46.1%) were non-smokers, 117 (33.9%) and 69 (20%) were current tobacco smokers with, respectively, low and severe nicotine dependence. In a multivariate model, CPI remained associated with severe NIC dependence (29 vs 15%, OR = 2.8, p = 0.003) and body mass index (OR = 1.1, p < 0.0001), independently of socio-demographic characteristics and antidepressant intake. No association of CPI with low to moderate tobacco smoking dependence, number of daily smoked cigarettes, cannabis use, alcohol use or illness characteristics was found (all p > 0.05). CPI was associated with severe NIC dependence but not with tobacco smoking with low to moderate NIC dependence in SZ, independently of socio-demographic variables, body mass index, alcohol consumption and antidepressant intake. This result highlights the potential CPI consequences of the high prevalence of heavy tobacco smoking in SZ, indicating the

  17. 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…

  18. The development and expression of physical nicotine dependence corresponds to structural and functional alterations in the anterior cingulate-precuneus pathway

    PubMed Central

    Huang, Wei; King, Jean A; Ursprung, W W Sanouri; Zheng, Shaokuan; Zhang, Nanyin; Kennedy, David N; Ziedonis, Douglas; DiFranza, Joseph R

    2014-01-01

    Introduction Perturbations in neural function provoked by a drug are thought to induce neural adaptations, which, in the absence of the drug, give rise to withdrawal symptoms. Previously published structural data from this study indicated that the progressive development of physical dependence is associated with increasing density of white matter tracts between the anterior cingulum bundle and the precuneus. Methods Using functional magnetic resonance imaging, we compared 11 smokers after 11 h of abstinence from nicotine and after satiation, with 10 nonsmoking controls, using independent component analysis for brain network comparisons as well as a whole brain resting-state functional connectivity analysis using the anterior cingulate cortex as a seed. Results Independent component analysis demonstrated increased functional connectivity in brain networks such as the default mode network associated with the withdrawal state in multiple brain regions. In seed-based analysis, smokers in the withdrawal state showed stronger functional connectivity than nonsmoking controls between the anterior cingulate cortex and the precuneus, caudate, putamen, and frontal cortex (P < 0.05). Among smokers, compared to the satiated state, nicotine withdrawal was associated with increased connectivity between the anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus, superior frontal gyrus, posterior cingulate cortex, superior temporal, and inferior temporal lobe (P < 0.02). The intensity of withdrawal-induced craving correlated with the strength of connectivity between the anterior cingulate cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (r = 0.60–0.76; P < 0.05). Conclusions In concordance with our previous report that structural neural connectivity between the anterior cingulate area and the precuneus increased in proportion to the progression of physical dependence, resting-state functional connectivity in this

  19. Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning.

    PubMed

    Gould, Thomas J; Leach, Prescott T

    2014-01-01

    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

  20. 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

  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. 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.

  3. Treating nicotine dependence by targeting attention deficit hyperactivity disorder (ADHD): The role of ADHD severity and treatment response in a randomized controlled trial

    PubMed Central

    Nunes, Edward V.; Covey, Lirio S.; Brigham, Gregory; Hu, Mei-Chen; Levin, Frances R.; Somoza, Eugene; Winhusen, Theresa

    2014-01-01

    Objective To determine whether treatment of ADHD with osmotic-release oral system methylphenidate (OROS-MPH) promotes abstinence from smoking among ADHD-smokers with greater severity of ADHD symptoms at baseline, or greater improvement in ADHD during treatment. Method A randomized, double-blind, 11-week trial, was conducted between December 2005 and January 2008 at six clinical sites, sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers, meeting DSM-IV criteria for ADHD, were randomly assigned to OROS-MPH (72 mg/day) (N = 127) or matching placebo (N = 128). All participants received nicotine patch (21 mg) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline DSM-IV ADHD Rating Scale (ADHD-RS) score, change in ADHD-RS during treatment, and their interactions. Results Treatment interacted with both ADHD-RS at baseline (p=0.01), and with change in ADHD-RS during treatment (p=0.008). Among patients with higher ADHD-RS scores (>36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ≥24), 70% achieved abstinence on OROS-MPH, compared to 37% on placebo (p=.02). In contrast, among patients with the lowest ADHD-RS baseline scores (≤ 30), 30% achieved abstinence on OROS-MPH, compared to 61% on placebo (p=.02). Conclusions OROS-MPH, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD, and more robust response of ADHD symptoms to the medication. OROS-MPH may be counterproductive among smokers with lower severity of ADHD. PMID:24229749

  4. Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: Implications for teenage smoking

    PubMed Central

    Carcoba, Luis M.; Orfila, James E.; Natividad, Luis A.; Torres, Oscar V.; Pipkin, Joseph A.; Ferree, Patrick L.; Castañeda, Eddie; Moss, Donald E.; O’Dell, Laura E.

    2014-01-01

    Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats as compared to 1) adolescents and 2) adults that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAcc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (PND 28–42) and adult rats (PND 60–74) were prepared with osmotic pumps that delivered nicotine for 14 days (4.7 mg/kg/day adolescents; 3.2 mg/kg/day adults). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, rats were implanted with microdialysis probes in the NAcc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic-receptor antagonist mecamylamine (1.5 mg/kg and 3.0 mg/kg, IP) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAcc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During nicotine withdrawal, ACh levels in

  5. Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

    PubMed

    Carcoba, Luis M; Orfila, James E; Natividad, Luis A; Torres, Oscar V; Pipkin, Joseph A; Ferree, Patrick L; Castañeda, Eddie; Moss, Donald E; O'Dell, Laura E

    2014-01-01

    Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During

  6. 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.

  7. Discriminative stimulus effects of nicotine in humans.

    PubMed

    Perkins, Kenneth A

    2009-01-01

    Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. Men may be more sensitive than women to nicotine's discriminative stimulus effects, consistent with other research suggesting that nicotine is more reinforcing in men than in women. Other potential individual differences in nicotine discrimination have not been clearly tested, but may include genetics, obesity, and dependence on other drugs. Acute environmental factors that alter nicotine discrimination include the specific training and testing conditions, pointing to the need for careful control over such conditions during research. Other factors, such as concurrent acute use of alcohol or caffeine, do not appear to alter nicotine discrimination, suggesting that changes in nicotine discrimination are not likely explanations for the association of smoking behavior with use of those drugs. Concurrent physical activity also does not appear to alter nicotine discrimination, indicating that results from studies of discrimination in

  8. Threshold of adulthood for the onset of nicotine self-administration in male and female rats.

    PubMed

    Levin, Edward D; Slade, Susan; Wells, Corinne; Cauley, Marty; Petro, Ann; Vendittelli, Analise; Johnson, Michael; Williams, Paul; Horton, Kofi; Rezvani, Amir H

    2011-12-01

    The great majority of tobacco addiction begins during adolescence. More heavily addicted smokers begin smoking earlier, but differentiating the neurobehavioral impact of nicotine self-administration during adolescence from self-selection bias (whereby people more prone to heavy addiction also begin earlier) cannot be ethically unconfounded in humans. The goals of this research were to determine the age threshold for the adult-like nicotine self-administration and determine sex differences. Male and female Sprague-Dawley rats were tested for nicotine self-administration starting at 4, 5, 6, 7, and 8 weeks of age in an operant FR1 schedule for IV nicotine (0.03 mg/kg/infusion) in 45-min sessions for 2 weeks, with 1 week of enforced abstinence and 1 week of resumed access. This study replicated our earlier work that nicotine self-administration was increased in adolescent vs. adult rats and that the effect was more pronounced in adolescent males, but the increased nicotine self-administration was more persistent in adolescent-onset females. The age threshold for adult-like behavior was 6-7 weeks of age. Adolescent-onset nicotine self-administration had persisting effects of eggaurated increases of nicotine self-administration when fixed-ratio requirements for self-administration were lowered. Female rats that had begun nicotine self-administration during adolescence showed exaggerated increases in nicotine self-administration after a switch back to FR1 from FR8, indicating a lessened control over their self-administration. Adolescent-onset nicotine self-administration was not found to potentiate cocaine self-administration. Adolescent-onset nicotine self-administration causes persistent increases in nicotine self-administration in female rats even after they reach adulthood and disrupts control over self-administration behavior.

  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. Subjective effects of transdermal nicotine among nonsmokers.

    PubMed

    Ashare, Rebecca L; Baschnagel, Joseph S; Hawk, Larry W

    2010-04-01

    The subjective experience of nicotine, which may be influenced by personality traits as well as environmental factors, may be important for understanding the factors associated with the initiation and maintenance of nicotine dependence. The present study examined the effects of 7 mg transdermal nicotine among a relatively large sample (n = 91; 44 women) of college-aged nonsmokers. Using a placebo controlled, double-blind, within-subjects design, nicotine's effects were examined at rest and again after participants completed a sustained attention task. Sex and personality factors (Behavioral Inhibition and Behavioral Approach; BIS/BAS Scales; Carver & White, 1994) were examined as potential moderators. Overall, the effects of nicotine were generally modest and unpleasant. In the context of the cognitive task, nicotine increased nausea and negative affect but reduced fatigue, relative to placebo. In contrast, effects of nicotine during the initial 4 hr of patch administration, in which participants were in their natural environments, were moderated by individual differences in behavioral approach. Neither behavioral inhibition nor gender reliably moderated any subjective effects of nicotine. The present work suggests transdermal nicotine exerts only modest, mostly negative effects among nonsmokers. Future work should examine both contextual and personality moderators in large samples of participants who are exposed to nicotine through multiple routes of administration.

  11. 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.

  12. Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.

    PubMed

    Morris, S A; Kelso, M L; Liput, D J; Marshall, S A; Nixon, K

    2010-02-01

    Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on

  13. Psychiatric Syndromes in Adolescents with Marijuana Abuse and Dependency in Outpatient Treatment

    ERIC Educational Resources Information Center

    Diamond, Guy; Panichelli-Mindel, Susan M.; Shera, David; Dennis, Mike; Tims, Frank; Ungemack, Jane

    2006-01-01

    Objective: The purpose of the current study to assist in understanding the prevalence and clinical correlates of psychiatric distress in adolescents seeking outpatient services for marijuana abuse or dependency. Methods: In a multi-site randomized clinical trial, 600 adolescents and their parents were assessed at intake using the Global Appraisals…

  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. Public Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke.

    PubMed

    Farber, Harold J; Nelson, Kevin E; Groner, Judith A; Walley, Susan C

    2015-11-01

    Tobacco use and tobacco smoke exposure are among the most important health threats to children, adolescents, and adults. There is no safe level of tobacco smoke exposure. The developing brains of children and adolescents are particularly vulnerable to the development of tobacco and nicotine dependence. Tobacco is unique among consumer products in that it causes disease and death when used exactly as intended. Tobacco continues to be heavily promoted to children and young adults. Flavored and alternative tobacco products, including little cigars, chewing tobacco, and electronic nicotine delivery systems are gaining popularity among youth. This statement describes important evidence-based public policy actions that, when implemented, will reduce tobacco product use and tobacco smoke exposure among youth and, by doing so, improve the health of children and young adults.

  16. 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…

  17. Neuronal nicotinic acetylcholine receptors are modulated by zinc.

    PubMed

    Vázquez-Gómez, Elizabeth; García-Colunga, Jesús

    2009-01-01

    It is known that zinc modulates nicotinic acetylcholine receptors (nAChRs). Here, we studied the effects of zinc on neuronal alpha4beta4 nAChRs, expressed in Xenopus oocytes and activated by nicotine. Membrane ion currents elicited by nicotine (10 nM to 100 microM) were enhanced by zinc (100 microM). Maximal zinc potentiation of the nicotine-activated current (2530%) occurred at 50 nM nicotine, and potentiation gradually decreased as the nicotine concentration increased. The EC(50) and IC(50) for the nicotine-activated current were 639 nM and 14.7 microM nicotine, respectively. Both parameters decreased in the presence of zinc to 160 nM and 4.6 microM, respectively, probably due to an increase of sensitivity of nAChRs for nicotine. We used different concentrations and durations of exposure to nicotine, due to desensitization of nAChRs directly depends on both these factors. With 500 nM nicotine and 20 min washing periods between nicotine applications, zinc potentiation remained constant, 901% for 2 min and 813% for 20 min of nicotine exposure. With continuous application of nicotine, zinc potentiation decreased as the time of nicotine exposure increased, 721% for 2 min and 254% for 48 min of nicotine exposure. Our results indicate that zinc-potentiating effects on alpha4beta4 nAChRs strongly depend on both concentration and time of exposure to nicotine, suggesting that zinc potentiation depends on the degree of desensitization.

  18. Age-dependent changes in the functional expression of two nicotinic receptor subtypes in CA1 stratum radiatum interneurons in the rat hippocampus.

    PubMed

    Alkondon, Manickavasagom; Pereira, Edna F R; Albuquerque, Edson X

    2007-10-15

    Protein density measurements and mRNA analysis have provided valuable information on age-dependent changes in the distribution of different nicotinic receptor (nAChR) subtypes in various areas of the rat brain, including the hippocampus. However, very little is known regarding the functional expression of nAChRs in individual neuron types at various ages. Likewise, there is paucity of information regarding the functional and pharmacological profile of nAChRs in the mature rat hippocampus. To address these issues, we used the whole-cell patch-clamp technique to record nicotinic responses from CA1 stratum radiatum (SR) interneurons in hippocampal slices from rat pups (5-19 days old) and adult rats (2-5 months old). As previously observed in the hippocampus of rat pups, CA1 SR interneurons in the hippocampus of adult rats responded to choline (10mM, 12s) with whole-cell currents that decayed to the baseline within the agonist pulse, were sensitive to inhibition by methyllycaconitine (10nM) or alpha-bungarotoxin (50 nM), and were, therefore, mediated by alpha7*(1)[1] nAChRs. Likewise, as previously observed in the hippocampus of young rats, in the adult rat hippocampus excitatory postsynaptic currents (EPSCs) were recorded from SR interneurons in response to a pulse of ACh (0.1 mM, 12s) applied in the presence of the GABA(A) receptor antagonist bicuculline. ACh-triggered EPSCs were inhibited by mecamylamine (1 microM) or choline (1 mM) and were, therefore, likely to have resulted from activation of alpha3beta4beta2* nAChR. The magnitude of alpha7* nAChR-mediated responses increased with the age of the animals. In contrast, the magnitude of alpha3beta4beta2* nAChR-mediated responses was highest at the second postnatal week. The distinct age dependency of functional expression of alpha7* and alpha3beta4beta2* nAChRs strongly suggests that the excitability of CA1 SR interneurons is differentially regulated by the nicotinic cholinergic system in the hippocampus of rat pups

  19. The magnitude of alpha7 nicotinic receptor currents in rat hippocampal neurons is dependent upon GABAergic activity and depolarization.

    PubMed

    Santos, Hélio R; Ribeiro, Helizane S; Setti-Perdigão, Pedro; Albuquerque, Edson X; Castro, Newton G

    2006-10-01

    Hippocampal alpha7(*) nicotinic acetylcholine receptors modulate the release of GABA and glutamate. The control of functional receptor pools by cell firing or synaptic activity could therefore allow for a local adjustment of the sensitivity to cholinergic input upon changes in neuronal activity. We first investigated whether tonic depolarization or cell firing affected the function of alpha7(*). The amplitude of alpha7(*)-gated whole-cell currents in cultured rat hippocampal neurons exposed to high-extracellular K(+) (40 mM KCl) for 24 to 48 h increased 1.3 to 5.5 times. The proportion of alpha7(*)-responsive neurons (99%), the potency of acetylcholine, and the sensitivity to nicotinic antagonists were all unaffected. In contrast, block of spontaneous cell firing with tetrodotoxin for 24 h led to a 37% reduction in mean current amplitude. Reduced alpha7(*) responses were seen after a 24-h blockade of N-type calcium channels but not of L-type calcium channels, N-methyl-d-aspartate (NMDA), or non-NMDA receptor channels, protein kinase C, or calcium-calmodulin kinases II and IV. The N-type or L-type calcium channel antagonists omega-conotoxin GVIA and nifedipine did not prevent the current-potentiating effect of KCl. The GABA(A) antagonist picrotoxin led to a 44% reduction of the currents, despite increasing action potential firing, and also reversed the potentiating effect of KCl. Treatment with GABA, midazolam, or a GABA uptake blocker led to increased currents. These data indicate that alpha7(*)-gated currents in hippocampal neurons are regulated by GABAergic activity and suggest that depolarization-induced GABA release may underlie the effect of increased extracellular KCl.

  20. The CB1 Neutral Antagonist AM4113 Retains the Therapeutic Efficacy of the Inverse Agonist Rimonabant for Nicotine Dependence and Weight Loss with Better Psychiatric Tolerability

    PubMed Central

    Gueye, Aliou B.; Pryslawsky, Yaroslaw; Trigo, Jose M.; Poulia, Nafsika; Delis, Foteini; Antoniou, Katerina; Loureiro, Michael; Laviolette, Steve R.; Vemuri, Kiran; Makriyannis, Alexandros

    2016-01-01

    Background: Multiple studies suggest a pivotal role of the endocannabinoid system in regulating the reinforcing effects of various substances of abuse. Rimonabant, a CB1 inverse agonist found to be effective for smoking cessation, was associated with an increased risk of anxiety and depression. Here we evaluated the effects of the CB1 neutral antagonist AM4113 on the abuse-related effects of nicotine and its effects on anxiety and depressive-like behavior in rats. Methods: Rats were trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio schedules of reinforcement. A control group was trained to self-administer food. The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine taking, motivation for nicotine, and cue-, nicotine priming- and yohimbine-induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal firing and bursting activity of midbrain dopamine neurons were evaluated in a separate group of animals treated with nicotine. Anxiety/depression-like effects of AM4113 and rimonabant were evaluated 24h after chronic (21 days) pretreatment (0, 1, 3, and 10mg/kg, 1/d). Results: AM4113 significantly attenuated nicotine taking, motivation for nicotine, as well as cue-, priming- and stress-induced reinstatement of nicotine-seeking behavior. These effects were accompanied by a decrease of the firing and burst rates in the ventral tegmental area dopamine neurons in response to nicotine. On the other hand, AM4113 pretreatment did not have effects on operant responding for food. Importantly, AM4113 did not have effects on anxiety and showed antidepressant-like effects. Conclusion: Our results indicate that AM4113 could be a promising therapeutic option for the prevention of relapse to nicotine-seeking while lacking anxiety/depression-like side effects. PMID:27493155

  1. Effects of Intraoperative Dexmedetomidine on Postoperative Pain in Highly Nicotine-Dependent Patients After Thoracic Surgery: A Prospective, Randomized, Controlled Trial.

    PubMed

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

    2016-05-01

    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.

  2. 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

  3. 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

  4. 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.

  5. Adolescent inpatient girls׳ report of dependent life events predicts prospective suicide risk.

    PubMed

    Stone, Lindsey B; Liu, Richard T; Yen, Shirley

    2014-09-30

    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.

  6. Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FKBP5

    PubMed Central

    Handley, Elizabeth D.; Rogosch, Fred A.; Cicchetti, Dante

    2015-01-01

    The current study examined the prospective association between child maltreatment and the development of substance use disorder (SUD) 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 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 1–2 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 SUD in adolescence is dependent on FKBP5 genetic variation. PMID:26535939

  7. Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

    PubMed

    Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B

    2016-01-01

    Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences.

  8. 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

  9. 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

  10. Adolescent brain maturation and smoking: what we know and where we're headed.

    PubMed

    Lydon, David M; Wilson, Stephen J; Child, Amanda; Geier, Charles F

    2014-09-01

    Smoking is a leading cause of mortality and morbidity worldwide. Smoking initiation often occurs during adolescence. This paper reviews and synthesizes adolescent development and nicotine dependence literatures to provide an account of adolescent smoking from onset to compulsive use. We extend neurobiological models of adolescent risk-taking, that focus on the interplay between incentive processing and cognitive control brain systems, through incorporating psychosocial and contextual factors specific to smoking, to suggest that adolescents are more vulnerable than adults to cigarette use generally, but that individual differences exist placing some adolescents at increased risk for smoking. Upon smoking, adolescents are more likely to continue smoking due to the increased positive effects induced by nicotine during this period. Continued use during adolescence, may be best understood as reflecting drug-related changes to neural systems underlying incentive processing and cognitive control, resulting in decision-making that is biased towards continued smoking. Persistent changes following nicotine exposure that may underlie continued dependence are described. We highlight ways that interventions may benefit from a consideration of cognitive-neuroscience findings.

  11. 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.…

  12. Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66(shc)-dependent antioxidant responses.

    PubMed

    Arany, Istvan; Carter, Anthony; Hall, Samuel; Fulop, Tibor; Dixit, Mehul

    2017-02-01

    Chronic nicotine exposure (via smoking, E-cigarettes) increases oxidative stress in the kidney that sensitizes it to additional injury in experimental models and in the renal patient. The pro-apoptotic p66(shc) protein-via serine36 phosphorylation that facilitates its mitochondrial translocation and therein cytochrome c binding-generates oxidative stress that leads to injury of renal proximal tubule cells during chronic nicotine exposure. Coenzyme Q10-a clinically safe antioxidant-has been used against nicotine/smoke extract-associated oxidative stress in various non-renal cells. This study explored the anti-oxidant/anti-apoptotic effect of Coenzyme Q10 on nicotine-induced oxidative stress and its impact on p66shc in cultured rat renal proximal tubule cells (NRK52E). We studied the anti-oxidant effect of 10 µM Coenzyme Q10 using various mutants of the p66shc gene and also determined the induction of selected anti-oxidant entities (antioxidant response element, promoter of the manganese superoxide dismutase gene) in reporter luciferase assay during oxidative stress induced by 200 µM nicotine. Our studies revealed that Coenzyme Q10 strongly inhibits nicotine-mediated production of reactive oxygen species and consequent apoptosis that requires serine36 phosphorylation but not mitochondrial translocation/cytochrome c binding of p66(shc). While both nicotine and Coenzyme Q10 stimulates the p66shc promoter, only nicotine exposure results in mitochondrial translocation of p66(shc). In contrast, the Coenzyme Q10-stimulated and non-mitochondrial p66(shc) activates the anti-oxidant manganese superoxide dismutase promoter via the antioxidant response elements and hence, rescues cells from nicotine-induced oxidative stress and consequent apoptosis.

  13. Adolescent brain activation: dependence on sex, dietary satiation, and restraint.

    PubMed

    Varley-Campbell, Joanna L; Fulford, Jonathan; Moore, Melanie S; Williams, Craig A

    2017-03-30

    The study aimed to explore how both sex and dietary restraint impacts brain activation in response to visual food stimuli in young adolescents (12-13 years) under fed and fasted conditions. Food and non-food images were viewed by 15 boys and 14 girls, while functional magnetic resonance images were acquired. The adolescents were either fasted or in a satiated (fed) state following a randomized crossover study design. When satiation state was not considered, girls showed significantly greater brain activity than boys in regions associated with executive function and decision making, working memory, and self-awareness. In contrast, when either fasted or fed states were considered separately, boys showed significantly increased brain activity in regions linked to executive function, self-awareness, and decision making than the girls. When fasted, compared to unrestrained eaters, restrained individuals showed heightened activation in regions connected to executive function and decision making, with areas associated with self-assessment showing increased activity for unrestrained eaters relative to restrained under fed conditions. These findings highlight important differences in adolescent brain activity and support further investigations to gain greater insight into how these differences might evolve with age.

  14. Significant association of catechol-O-methyltransferase (COMT) haplotypes with nicotine dependence in male and female smokers of two ethnic populations.

    PubMed

    Beuten, Joke; Payne, Thomas J; Ma, Jennie Z; Li, Ming D

    2006-03-01

    The catechol-O-methyltransferase (COMT) gene plays a prominent role in dopaminergic circuits central to drug reward. Allelic variants within the COMT gene are therefore potential candidates for examining interindividual differences in vulnerability to nicotine dependence (ND). We analyzed five single nucleotide polymorphisms (SNPs), including the Val/Met variant (rs4680), which results in a three- to four-fold difference in enzyme activity within COMT, for association with the three ND measures, SQ, HSI, and FTND, in 602 nuclear families of African-American (AA) or European-American (EA) origin. The Val/Met variant showed a significant association with the three ND measures in the pooled and EA samples and with FTND in the AA sample. Haplotype analysis revealed a major protective A-G-T haplotype (frequency 23.6%) for rs740603-rs4680-rs174699 in the AA sample (minimum Z=-3.35; P=0.0005 for FTND), a major protective T-G-T haplotype (frequency 15.2%; minimum Z=-2.92; P=0.003 for FTND) in the EA sample, and a high-risk C-A-T haplotype (frequency 16.9%; minimum Z=3.16; P=0.002 for SQ) in the AA sample for rs933271-rs4680-rs174699. Furthermore, we found that the significant haplotypes within COMT were gender-specific and the significantly associated A-G-T is protective in AA females only, whereas T-G-T is protective in EA males only. Moreover, we found a major high-risk T-A-T haplotype (frequency 56.7%) that showed significant association with the three ND measures in EA males. Further examination of two protective haplotypes, A-G-T in AAs and T-G-T in EAs, indicated that the low COMT enzyme activity Met allele is protective to become nicotine dependent. In summary, our results provide evidence for a role of COMT in the susceptibility to ND and further confirm that its effect is ethnic and gender specific.

  15. 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

  16. Nicotine decreases the activity of glutamate transporter type 3.

    PubMed

    Yoon, Hea-Jo; Lim, Young-Jin; Zuo, Zhiyi; Hur, Wonseok; Do, Sang-Hwan

    2014-02-10

    Nicotine, the main ingredient of tobacco, elicits seizures in animal models and cigarette smoking is regarded as a behavioral risk factor associated with epilepsy or seizures. In the hippocampus, the origin of nicotine-induced seizures, most glutamate uptake could be performed primarily by excitatory amino acid transporter type 3 (EAAT3). An association between temporal lobe epilepsy and EAAT3 downregulation has been reported. Therefore, we hypothesized that nicotine may elicit seizures through the attenuation of EAAT3 activity. We investigated chronic nicotine exposure (72 h) cause reduction of the activity of EAAT3 in a Xenopus oocyte expression system using a two-electrode voltage clamp. The roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) were also determined. Nicotine (0.001-1 μM) resulted in a time- and dose-dependent decrease in EAAT3 activity with maximal inhibition at nicotine concentrations of 0.03 μM or higher and at an exposure time of 72 h. Vmax on the glutamate response was significantly reduced in the nicotine group (0.03 μM for 72 h), but the Km value of EAAT3 for glutamate was not altered. When nicotine-exposed oocytes (0.03 μM for 72 h) were pretreated with phorbol-12-myristate-13-acetate (PMA, a PKC activator), the nicotine-induced reduction in EAAT3 activity was abolished. PKC inhibitors (staurosporine, chelerythrine, and calphostin C) significantly reduced basal EAAT3 activity, but there were no significant differences among the PKC inhibitors, nicotine, and PKC inhibitors+nicotine groups. Similar response patterns were observed among PI3K inhibitors (wortmannin and LY294002), nicotine, and PI3K inhibitors+nicotine. In conclusion, this study suggests that nicotine decreases EAAT3 activity, and that this inhibition seems to be dependent on PKC and PI3K. Our results may provide an additional mechanism for nicotine-induced seizure.

  17. The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: Dual role in nicotine addiction and lung cancer

    PubMed Central

    Improgo, Ma. Reina D.; Scofield, Michael D.; Tapper, Andrew R.; Gardner, Paul D.

    2010-01-01

    More than 1 billion people around the world smoke, with 10 million cigarettes sold every minute. Cigarettes contain thousands of harmful chemicals including the psychoactive compound, nicotine. Nicotine addiction is initiated by the binding of nicotine to nicotinic acetylcholine receptors, ligand-gated cation channels activated by the endogenous neurotransmitter, acetylcholine. These receptors serve as prototypes for all ligand-gated ion channels and have been extensively studied in an attempt to elucidate their role in nicotine addiction. Many of these studies have focused on heteromeric nicotinic acetylcholine receptors containing α4 and β2 subunits and homomeric nicotinic acetylcholine receptors containing the α7 subunit, two of the most abundant subtypes expressed in the brain. Recently however, a series of linkage analyses, candidate-gene analyses and genome-wide association studies have brought attention to three other members of the nicotinic acetylcholine receptor family: the α5, α3 and β4 subunits. The genes encoding these subunits lie in a genomic cluster that contains variants associated with increased risk for several diseases including nicotine dependence and lung cancer. The underlying mechanisms for these associations have not yet been elucidated but decades of research on the nicotinic receptor gene family as well as emerging data provide insight on how these receptors may function in pathological states. Here, we review this body of work, focusing on the clustered nicotinic acetylcholine receptor genes and evaluating their role in nicotine addiction and lung cancer. PMID:20685379

  18. Dopamine genes and reward dependence in adolescents with excessive internet video game play.

    PubMed

    Han, Doug Hyun; Lee, Young Sik; Yang, Kevin C; Kim, Eun Young; Lyoo, In Kyoon; Renshaw, Perry F

    2007-09-01

    Excessive internet video game play (EIGP) has emerged as a leading cause of behavioral and developmental problems in adolescents. Recent research has implicated the role of striatal dopaminergic system in the behavioral maladaptations associated with EIGP. This study investigates the reward-dependence characteristics in EIGP adolescents as it potentially relates to genetic polymorphisms of the dopaminergic system and temperament. Seventy-nine male EIGP adolescents and 75 age- and gender-matched healthy comparison adolescents were recruited. Associations were tested with respect to the reward-dependence (RD) scale in Cloninger's Temperament and Character Inventory and the frequencies of 3 dopamine polymorphisms: Taq1A1 allele of the dopamine D2 receptor (DRD2 Taq1A1) and Val158Met in the Catecholamine-O-Methyltransferase (COMT) genes. The Taq1A1 and low activity (COMT) alleles were significantly more prevalent in the EIGP group relative to the comparison group. The present EIGP group had significantly higher RD scores than controls. Within the EIGP group, the presence of the Taq1A1 allele correlated with higher RD scores. Our findings suggest that EIGP subjects have higher reward dependency and an increased prevalence of the DRD2 Taq1A1 and COMT alleles. In particular, the DRD2 Taq1A1 allele seems to be associated with reward dependence in EIGP adolescents.

  19. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence.

    PubMed

    Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E

    2015-03-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.

  20. 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…

  1. 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…

  2. Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study.

    PubMed

    Schnoll, Robert A; Patterson, Freda; Wileyto, E Paul; Tyndale, Rachel F; Benowitz, Neal; Lerman, Caryn

    2009-03-01

    Transdermal nicotine is widely used for smoking cessation, but only approximately 20% of smokers quit successfully with this medication. Interindividual variability in nicotine metabolism rate may influence treatment response. This study sought to validate, and extend in a larger sample, our previous finding that the ratio of plasma nicotine metabolites 3'-hydroxycotinine (3-HC)/cotinine, a measure of nicotine metabolism rate, predicts response to nicotine patch. A sample of 568 smokers was enrolled in a study that provided counseling and 8-weeks of 21 mg nicotine patch. Pretreatment 3-HC/cotinine ratio was examined as a predictor of 7-day point prevalence abstinence, verified with breath carbon monoxide (CO), 8 weeks after the quit date. Controlling for sex, race, age, and nicotine dependence, smokers in the upper 3 quartiles of 3-HC/cotinine ratio (faster metabolizers) were approximately 50% less likely to be abstinent vs. smokers in the first quartile (slow metabolizers; 28% vs. 42%; OR=.54 [95% CI:.36-.82], p=.003). Among abstainers, plasma nicotine levels (assessed 1 week after treatment began) decreased linearly across the 3-HC/cotinine ratio (beta=-3.38, t[355]=-3.09, p<.05). These data support the value of the 3-HC/cotinine ratio as a biomarker to predict success with transdermal nicotine for smoking cessation.

  3. Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

    PubMed

    Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

    2013-12-01

    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 (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and 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 they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

  4. Nicotine replacement therapy

    MedlinePlus

    ... takes for the patch to work. The inhaler satisfies oral urges. Most of the nicotine vapor does ... spray provides a quick dose of nicotine to satisfy a craving you are unable to ignore. Levels ...

  5. Effects of Chronic Buspirone Treatment on Nicotine and Concurrent Nicotine+Cocaine Self-Administration

    PubMed Central

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J

    2013-01-01

    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

  6. 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.

  7. Correlates of interpersonal dependency and detachment in an adolescent inpatient sample.

    PubMed

    Haggerty, Greg; Siefert, Caleb J; Bornstein, Robert F; Sinclair, Samuel Justin; Blais, Mark A; Zodan, Jennifer; Rao, Nyapati

    2015-01-01

    Interpersonal dependency has been linked to psychological distress, depression, help seeking, treatment compliance, and sensitivity to interpersonal cues in adult samples. However, there is a dearth of research focusing on dependency in child and adolescent samples. The current study examined the construct validity of a measure of interpersonal dependency. The authors investigated how interpersonal dependency and detachment relate to behavioral problems, subjective well-being, interpersonal problems, and global symptom severity in adolescent inpatients. Destructive overdependence (DO) and dysfunctional detachment (DD) were positively related to interpersonal distress, behavioral problems, and symptom severity and negatively related to psychological health and well-being. Healthy dependency (HD) was associated with fewer behavioral problems and less symptom severity and positively related to subjective well-being. The clinical implications of these findings are discussed.

  8. 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

  9. Nicotine enhancement of dopamine release by a calcium-dependent increase in the size of the readily releasable pool of synaptic vesicles.

    PubMed

    Turner, Timothy J

    2004-12-15

    A major factor underlying compulsive tobacco use is nicotine-induced modulation of dopamine release in the mesolimbic reward pathway (Wise and Rompre, 1989). An established biochemical mechanism for nicotine-enhanced dopamine release is by activating presynaptic nicotinic acetylcholine receptors (nAChRs) (Wonnacott, 1997). Prolonged application of 10(-7) to 10(-5) m nicotine to striatal synaptosomes promoted a sustained efflux of [3H]dopamine. This nicotine effect was mediated by non-alpha7 nAChRs, because it was blocked by 5 mum mecamylamine but was resistant to 100 nm alpha-bungarotoxin (alphaBgTx). Dopamine release was diminished by omitting Na+ or by applying peptide calcium channel blockers, indicating that nAChRs trigger release by depolarizing the nerve terminals. However, because alpha7 receptors rapidly desensitize in the continuous presence of agonists, a repetitive stimulation protocol was used to evaluate the possible significance of desensitization. This protocol produced a transient increase in [3H]dopamine released by depolarization and a significant increase in the response to hypertonic solutions that measure the size of the readily releasable pool (RRP) of synaptic vesicles. The nicotine-induced increase in the size of the readily releasable pool was blocked by alphaBgTx and by the calmodulin antagonist calmidazolium, suggesting that Ca2+ entry through alpha7 nAChRs specifically enhances synaptic vesicle mobilization at dopamine terminals. Thus, nicotine enhances dopamine release by two complementary actions mediated by discrete nAChR subtypes and suggest that the alpha7 nAChR-mediated pathway is tightly and specifically coupled to refilling of the RRP of vesicles in dopamine terminals.

  10. Effect of the use-dependent, nicotinic receptor antagonist BTMPS in the forced swim test and elevated plus maze after cocaine discontinuation in rats.

    PubMed

    Hall, Brandon J; Pearson, Laura S; Buccafusco, Jerry J

    2010-04-26

    Withdrawal from cocaine use often is associated with anxiety and depressive states. In this study the use-dependent, nicotinic acetylcholine receptor antagonist bis-(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was studied for its ability to reduce these symptoms in two rat models of anxiety and depression. Rats were administered saline vehicle, or two escalating doses of cocaine, for a period of 5 days and they were evaluated during the period after cocaine discontinuation in the elevated plus maze (anxiety) and the forced swim test (affect). BTMPS (0.25, 0.5, or 0.75mg/kg) was co-administered with saline or cocaine in the dependence phase. Withdrawal from cocaine administration alone resulted in reductions in both the time spent in the open arms of the elevated plus maze test, as well as entries into, and out of, the open arms of the maze. Withdrawal from cocaine also resulted in a reduction of escape behaviors, and the time to first immobility, in the forced swim test. Treatment with BTMPS produced a reversal of cocaine-induced anxiety-like behaviors in the elevated plus maze, including an increase (up to 68%) in time spent in the open arms of the maze and an increase in the number of crossings between open and enclosed arms. BTMPS also reduced depressive-like behaviors associated with the forced swim test, including up to a 62% increase in the time to first immobility and a 50% increase in escape behavior. These results provide proof of concept for the development and use of cholinergic compounds in the treatment of substance abuse.

  11. 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

  12. 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…

  13. Baclofen prevents drug-induced reinstatement of extinguished nicotine-seeking behaviour and nicotine place preference in rodents.

    PubMed

    Fattore, Liana; Spano, Maria Sabrina; Cossu, Gregorio; Scherma, Maria; Fratta, Walter; Fadda, Paola

    2009-07-01

    The gamma-aminobutyric acid(GABA)-B receptor agonist baclofen is known to reduce drug intake in both animals and humans and to prevent reinstatement of cocaine-, opioid-, and alcohol-seeking in rats after a period of extinction, but its effect on nicotine reinstatement is unknown. This study investigated the effect of baclofen on nicotine-seeking reinstatement both using the extinction/reinstatement model of nicotine self-administration and conditioned place preference (CPP). Results showed that in rats previously trained to intravenously self-administer nicotine (30 microg/kg/inf) under a FR-1 schedule of reinforcement, acute nicotine (0.15 mg/kg) priming effectively reinstates nicotine-seeking behaviour following extinction. At doses used in this study (up to 2.5 mg/kg) baclofen alone did not affect locomotor activity and did not reinstate responding. However, baclofen dose-dependently attenuated drug-induced reinstatement of nicotine-seeking in rats. Moreover, baclofen (1.25 mg/kg) completely blocked nicotine-induced reinstatement of extinguished nicotine (0.3 mg/kg) CPP in mice. Altogether, our results showed that baclofen is able to antagonise reinstatement of nicotine-seeking and CPP triggered by nicotine primings, suggesting its potential clinical utility as an anti-relapse agent.

  14. 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.

  15. Effects of Chronic Varenicline Treatment on Nicotine, Cocaine, and Concurrent Nicotine+Cocaine Self-Administration

    PubMed Central

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

    2014-01-01

    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

  16. 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.

  17. 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…

  18. Sex Differences and the Effects of Stress on Subsequent Opioid Consumption in Adult Rats Following Adolescent Nicotine Exposure: A Psychopharmacologic Examination of the Gateway Hypothesis

    DTIC Science & Technology

    1997-07-18

    Chen, 1992; Newcomb & Bentler, 1986 ). Further, retrospective reports by Kandel and colleagues (Kandel & Yamaguchi, 1993; Kandel et al., 1992) indicate...animals suggest that there is a positive relationship between stress and substance abuse (Kosten, Rounsaville, & Kleber, 1986 ; O’Doherty, 1991; Shaham et...activation (Grunberg et al., 1997; USDHHS, 1988). Nicotine 9 administration also stimulates dopamine release from the ventral tegmental area ( Nisell

  19. Detoxification and elimination of nicotine by nectar-feeding birds.

    PubMed

    Lerch-Henning, S; Du Rand, E E; Nicolson, S W

    2017-02-01

    Many dilute nectars consumed by bird pollinators contain secondary metabolites, potentially toxic chemicals produced by plants as defences against herbivores. Consequently, nectar-feeding birds are challenged not only by frequent water excess, but also by the toxin content of their diet. High water turnover, however, could be advantageous to nectar consumers by enabling them to excrete secondary metabolites or their transformation products more easily. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences osmoregulation in white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens. We also examined the metabolic fate of nicotine in these two species to shed more light on the post-ingestive mechanisms that allow nectar-feeding birds to tolerate nectar nicotine. A high concentration of nicotine (50 µM) decreased cloacal fluid output and increased its osmolality in both species, due to reduced food intake that led to dehydration. White-eyes excreted a higher proportion of the ingested nicotine-containing diet than sunbirds. However, sugar concentration did not affect nicotine detoxification and elimination. Both species metabolised nicotine, excreting very little unchanged nicotine. Cape white-eyes mainly metabolised nicotine through the cotinine metabolic pathway, with norcotinine being the most abundant metabolite in the excreta, while white-bellied sunbirds excreted mainly nornicotine. Both species also utilized phase II conjugation reactions to detoxify nicotine, with Cape white-eyes depending more on the mercapturic acid pathway to detoxify nicotine than white-bellied sunbirds. We found that sunbirds and white-eyes, despite having a similar nicotine tolerance, responded differently and used different nicotine-derived metabolites to excrete nicotine.

  20. Parental Alcohol Dependence and the Transmission of Adolescent Behavioral Disinhibition: A Study of Adoptive and Non-Adoptive Families

    PubMed Central

    King, Serena M.; Keyes, Margaret; Malone, Stephen M.; Elkins, Irene; Legrand, Lisa N.; Iacono, William G.; McGue, Matt

    2009-01-01

    Aim To examine the genetic and environmental influences of parental alcoholism on offspring disinhibited behavior. Design We compared the effect of parental alcoholism history on offspring in adoptive and non-adoptive families. In families with a history of parental alcohol dependence, we examined the effect of exposure to parental alcoholism symptoms during the lifetime of the adolescent. Setting Assessments occurred at the University of Minnesota from 1998-2004. Participants Adolescents adopted in infancy were systematically ascertained from records of three private Minnesota adoption agencies; non-adopted adolescents were ascertained from Minnesota birth records. Adolescents and their rearing parents participated in in-person assessments. Measurements For adolescents, measures included self- reports of delinquency, deviant peers, substance use, antisocial attitudes, and personality. For parents, we conducted DSM-IV clinical assessments of alcohol abuse and dependence. Findings A history of parental alcohol dependence was associated with higher levels of disinhibition only when adolescents were biologically related to their rearing parents. Within families with a history of parental alcoholism, exposure to parental alcohol misuse during the lifetime of the adolescent was associated with increased odds of using alcohol in adopted adolescents only. Conclusions These findings suggest that the association between a history of parental alcohol dependence and adolescent offspring behavioral disinhibition is largely attributable to genetic rather than environmental transmission. We also obtained some evidence for parental alcohol misuse as a shared environmental risk factor in adoptive families. PMID:19215604

  1. [Reconsideration of nicotine and other substance dependence: a clue from dependence-related mentation including reward, motivation, learning, delusion and hallucination toward understanding the concept of non-substance-related addiction].

    PubMed

    Miyata, Hisatsugu

    2013-11-01

    Nicotine produces core symptoms of substance dependence (craving and withdrawal) without any psychotic symptoms. The psychopharmacological structure of craving is hypothesized to be constituted by three components: the primary reinforcing property of a substance, the secondary reinforcing property of that substance (conditioned aspects of the environment, such as contextual or specific cues associated with substance taking), and the negative affective motivational property during withdrawal (i.e. the desire to avoid the dysphoric withdrawal symptoms elicits craving). Among the three components, the primary reinforcing property of a substance forms the most fundamental factor for establishing substance dependence. Sensitization or reverse tolerance observed in locomotor activity of animals, which had been believed to be a methamphetamine psychosis model, is demonstrated to reflect the establishment of conditioned reinforcement. Finally, non-substance-related addiction such as gambling, internet, and sex is discussed. From the aspect of the above hypothetical psychopharmacological structure of craving, the most significant difference between substance dependence and non-substance-related addiction is that the primary reinforcing property of non-substance reward is relatively intangible in comparison with that of a substance of abuse.

  2. [Nicotine effects on mitochondria membrane potential: participation of nicotinic acetylcholine receptors].

    PubMed

    Gergalova, G L; Skok, M V

    2011-01-01

    The effect of nicotine on the mouse liver mitochondria was studied by fluorescent flow cytometry. Mice consumed nicotine during 65 days; alternatively, nicotine was added to isolated mitochondria. Mitochondria of nicotine-treated mice had significantly lower basic levels of membrane potential and granularity as compared to those of the control group. Pre-incubation of the isolated mitochondria with nicotine prevented from dissipation of their membrane potential stimulated with 0.8 microM CaCl2 depending on the dose, and this effect was strengthened by the antagonist of alpha7 nicotinic receptors (alpha7 nAChR) methyllicaconitine. Mitochondria of mice intravenously injected with the antibodies against alpha7 nAChR demonstrated lower levels of membrane potential. Introduction of nicotine, choline, acetylcholine or synthetic alpha7 nAChR agonist PNU 282987 into the incubation medium inhibited Ca2+ accumulation in mitochondria, although the doses of agonists were too low to activate the alpha7 nAChR ion channel. It is concluded that nicotine consumption worsens the functional state of mitochondria by affecting their membrane potential and granularity, and this effect, at least in part, is mediated by alpha7 nAChR desensitization.

  3. Sex differences in nicotine action.

    PubMed

    Pogun, Sakire; Yararbas, Gorkem

    2009-01-01

    Accumulating evidence suggests that the antecedents, consequences, and mechanisms of drug abuse and dependence are not identical in males and females and that gender may be an important variable in treatment and prevention. Although there has been a decline in smoking prevalence in developed countries, females are less successful in quitting. Tobacco use is accepted to be a form of addiction, which manifests sex differences. There is also evidence for sex differences in the central effects of nicotine in laboratory animals. Although social factors impact smoking substantially in humans, findings from nonhuman subjects in controlled experiments provide support that sex differences in nicotine/tobacco addiction have a biological basis. Differences in the pharmacokinetic properties of nicotine or the effect of gonadal hormones may underlie some but not all sex differences observed. Laboratory-based information is very important in developing treatment strategies. Literature findings suggest that including sex as a factor in nicotine/tobacco-related studies will improve our success rates in individually tailored smoking cessation programs.

  4. Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence

    PubMed Central

    Yoon, Dankyu; Kim, Young-Jin; Cui, Wen-Yan; Van der Vaart, Andrew; Shin Cho, Yoon; Lee, Jong-Young; Ma, Jennie Z.; Payne, Thomas J.; Li, Ming D.; Park, Taesung

    2014-01-01

    Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p valuemeta = 6.40 × 10−6; rs2349433, p valuemeta = 5.57 × 10−6), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p valuemeta = 2.30 × 10−6) and the other at 7q31.1 (rs848353, p valuemeta = 9.16 × 10−8). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples. PMID:22006218

  5. Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.

    PubMed

    Yoon, Dankyu; Kim, Young-Jin; Cui, Wen-Yan; Van der Vaart, Andrew; Cho, Yoon Shin; Lee, Jong-Young; Ma, Jennie Z; Payne, Thomas J; Li, Ming D; Park, Taesung

    2012-06-01

    Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p value(meta) = 6.40 × 10(-6); rs2349433, p value(meta) = 5.57 × 10(-6)), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p value(meta) = 2.30 × 10(-6)) and the other at 7q31.1 (rs848353, p value(meta) = 9.16 × 10(-8)). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples.

  6. Hormones, nicotine, and cocaine: clinical studies.

    PubMed

    Mello, Nancy K

    2010-06-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (<20 min), ratings of "high" and "rush" began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.

  7. Hormones, Nicotine and Cocaine: Clinical Studies

    PubMed Central

    Mello, Nancy K.

    2009-01-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (< 20 min), ratings of “High” and “Rush” began to decrease within one or two puffs of a high nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

  8. Partitioning of Homologous Nicotinic Acid Ester Prodrugs (Nicotinates) into Dipalmitoylphosphatidylcholine (DPPC) Membrane Bilayers

    PubMed Central

    Ojogun, Vivian; Vyas, Sandhya M.; Lehmler, Hans-Joachim; Knutson, Barbara L

    2010-01-01

    The partitioning behavior of a series of perhydrocarbon nicotinic acid esters (nicotinates) between aqueous solution and dipalmitoylphosphatidylcholine (DPPC) membrane bilayers is investigated as a function of increasing alkyl chain length. The hydrocarbon nicotinates represent putative prodrugs, derivatives of the polar drug nicotinic acid, whose functionalization provides the hydrophobic character necessary for pulmonary delivery in a hydrophobic, fluorocarbon solvent, such as perfluorooctyl bromide. Independent techniques of differential scanning calorimetry and 1,6-diphenyl-1,3,5 hexatriene (DPH) fluorescence anisotropy measurements are used to analyze the thermotropic phase behavior and lipid bilayer fluidity as a function of nicotinate concentration. At increasing concentrations of nicotinates over the DPPC mole fraction range examined (XDPPC = 0.6 – 1.0), all the nicotinates (ethyl (C2H5); butyl (C4H9); hexyl (C6H13); and octyl (C8H17)) partition into the lipid bilayer at sufficient levels to eliminate the pretransition, and decrease and broaden the gel to fluid phase transition temperature. The concentration at which these effects occur is chain length-dependent; the shortest chain nicotinate, C2H5, elicits the least dramatic response. Similarly, the DPH anisotropy results demonstrate an alteration of the bilayer organization in the liposomes as a consequence of the chain length-dependent partitioning of the nicotinates into DPPC bilayers. The membrane partition coefficients (logarithm values), determined from the depressed bilayer phase transition temperatures, increase from 2.18 for C2H5 to 5.25 for C8H17. The DPPC membrane/water partitioning of the perhydrocarbon nicotinate series correlates with trends in the octanol/water partitioning of these solutes, suggesting that their incorporation into the bilayer is driven by increasing hydrophobicity. PMID:20227859

  9. Nicotine-morphine interactions at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors.

    PubMed

    Talka, Reeta; Salminen, Outi; Whiteaker, Paul; Lukas, Ronald J; Tuominen, Raimo K

    2013-02-15

    Nicotine and opioids share several behavioral and rewarding properties. Although both opioids and nicotine have their own specific mechanism of action, there is empirical and experimental evidence of interactions between these drugs. We studied receptor-level interactions of nicotine and morphine at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors. [(3)H]epibatidine displacement was used to determine if morphine binds competitively to nicotinic acetylcholine receptors. Functional interactions of morphine and nicotine were studied with calcium fluorometry and (86)Rb(+) efflux assays. Morphine displaced [(3)H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2μM in SH-EP1-hα4β2 cells, 0.16μM and 126μM in SH-SY5Y cells and 43.7μM in SH-EP1-hα7 cells. In SH-EP1-hα4β2 cells expressing α4β2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of (86)Rb(+) efflux comparable to cytisine (with EC50 values of 53.3μM for morphine and 5.38μM for cytisine). The effect of morphine was attenuated concentration-dependently by the nicotinic antagonist mecamylamine. In the SH-SY5Y cell line expressing several subtypes of nicotinic acetylcholine receptors morphine had an inhibitory effect on nicotine induced (86)Rb(+) ion efflux mediated by α3(⁎) nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at α4β2 nicotinic acetylcholine receptors and as a weak antagonist at α3(⁎) nicotinic acetylcholine receptors.

  10. 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.

  11. 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.

  12. Neurotensin agonist attenuates nicotine potentiation to cocaine sensitization.

    PubMed

    Fredrickson, Paul; Boules, Mona; Stennett, Bethany; Richelson, Elliott

    2014-03-01

    Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a "gateway drug". Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

  13. Transport Mechanism of Nicotine in Primary Cultured Alveolar Epithelial Cells.

    PubMed

    Takano, Mikihisa; Nagahiro, Machi; Yumoto, Ryoko

    2016-02-01

    Nicotine is absorbed from the lungs into the systemic circulation during cigarette smoking. However, there is little information concerning the transport mechanism of nicotine in alveolar epithelial cells. In this study, we characterized the uptake of nicotine in rat primary cultured type II (TII) and transdifferentiated type I-like (TIL) epithelial cells. In both TIL and TII cells, [(3)H]nicotine uptake was time and temperature-dependent, and showed saturation kinetics. [(3)H]Nicotine uptake in these cells was not affected by Na(+), but was sensitive to extracellular and intracellular pH, suggesting the involvement of a nicotine/proton antiport system. The uptake of [(3)H]nicotine in these cells was potently inhibited by organic cations such as clonidine, diphenhydramine, and pyrilamine, but was not affected by substrates and/or inhibitors of known organic cation transporters such as carnitine, 1-methyl-4-phenylpyridinium, and tetraethylammonium. In addition, the uptake of [(3)H]nicotine in TIL cells was stimulated by preloading the cells with unlabeled nicotine, pyrilamine, and diphenhydramine, but not with tetraethylammonium. These results suggest that a novel proton-coupled antiporter is involved in the uptake of nicotine in alveolar epithelial cells and its absorption from the lungs into the systemic circulation.

  14. Nicotine enhances contextual fear memory reconsolidation in rats.

    PubMed

    Tian, Shaowen; Huang, Fulian; Li, Peng; Li, Zhenbang; Zhou, Shouhong; Deng, Haifeng; Yang, Yufeng

    2011-01-10

    There is increasing evidence that nicotine is involved in learning and memory. However, there remains no study that has explored the relationship between nicotine and memory reconsolidation. At present study, we tested the effects of nicotine on the reconsolidation of contextual fear memory in rats. Behavior procedure involved four training phases: habituation (Day 0), fear conditioning (Day 1), reactivation (Day 2) and test (Day 3). Rats were injected saline or nicotine (0.25, 0.5 and 1.0mg/kg) immediately after reactivation. Percent of time spent freezing was used to measure conditioned fear response. Results showed that compared with saline rats, rats with nicotine at 1.0mg/kg presented a significant increase of freezing response on Day 3. Nicotine at 1.0mg/kg was ineffective when injected 6h after reactivation. Further results showed that the enhancement of freezing response induced by nicotine at 1.0mg/kg was dependent on fear memory reconsolidation, and was not attributed to an enhancement of the nonspecific freezing response 24h after nicotine administration. The results suggest that nicotine administration immediately after reactivation enhances contextual fear memory reconsolidation. Our present finding extends previous research on the nicotinic effects on learning and memory.

  15. 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.

  16. 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.

  17. 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.

  18. Increased Nicotine Self-Administration Following Prenatal Exposure in Female Rats

    PubMed Central

    Levin, Edward D.; Lawrence, Susan; Petro, Ann; Horton, Kofi; Seidler, Frederic J.; Slotkin, Theodore A.

    2007-01-01

    There is a significant association between maternal cigarette smoking during pregnancy and greater subsequent risk of smoking in female offspring. In animal models, prenatal nicotine exposure causes persistent alterations in cholinergic and monoaminergic systems, both of which are important for nicotine actions underlying tobacco addiction. Accordingly, the current study was conducted to determine if there is a cause-and-effect relationship between prenatal nicotine exposure and nicotine self-administration starting in adolescence. Pregnant rats were administered nicotine (6 mg/kg/day) by osmotic minipump infusion throughout gestation and then, beginning in adolescence and continuing into adulthood, female offspring were given access to nicotine via a standard operant IV self-administration procedure (0.03 mg/kg/infusion). Gestational nicotine exposure did not alter the initial rate of nicotine self-administration. However, when animals underwent one week of forced abstinence and then had a second opportunity to self-administer nicotine, the prenatally-exposed animals showed a significantly greater rate of self-administration than did the controls. Prenatal nicotine exposure causes increased nicotine self-administration, which is revealed only when the animals are allowed to experience a period of nicotine abstinence. This supports a cause-and-effect relationship between the higher rates of smoking in the daughters of women who smoke cigarettes during pregnancy and implicates a role for nicotine in this effect. Our results further characterize the long-term liabilities of maternal smoking but also point to the potential liabilities of nicotine-based treatments for smoking cessation during pregnancy. PMID:17196243

  19. 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.

  20. The Effect of Alcohol Abuse and Dependence and School Experiences on Depression: A National Study of Adolescents

    ERIC Educational Resources Information Center

    Merianos, Ashley L.; King, Keith A.; Vidourek, Rebecca A.; Hardee, Angelica M.

    2016-01-01

    The study purpose was to examine the effect alcohol abuse/dependence and school experiences have on depression among a nationwide sample of adolescents. A secondary analysis of the 2013 National Survey on Drug Use and Health was conducted. The results of the final multivariable logistic regression model revealed that adolescents who reported…

  1. 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…

  2. 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.

  3. Electronic Nicotine Delivery Systems.

    PubMed

    Walley, Susan C; Jenssen, Brian P

    2015-11-01

    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control.

  4. Chronic nicotine alters cannabinoid-mediated locomotor activity and receptor density in periadolescent but not adult male rats

    PubMed Central

    Werling, Linda L.; Reed, Stephanie Collins; Wade, Dean; Izenwasser, Sari

    2009-01-01

    A significant number of youths use cigarettes, and more than half of the youths who smoke daily also use illicit drugs. The focus of these studies is on how exposure to nicotine affects subsequent responses to both nicotine and cannabinoids in adolescents compared with adults. We have shown previously that chronic treatment with nicotine produces sensitization to its locomotor-activating effects in female and adult rats but not male adolescent rats. To better understand the effects of nicotine on adolescent and adult rats, rats were injected with nicotine or saline for 7 days and, on day 8, either challenged with delta-9-tetrahydrocannabinol (Δ9-THC) or the cannabinoid agonist CP 55,940 and tested for locomotor activity, or the brains were removed for quantitative autoradiography studies of the cannabinoid1 receptor. A separate group of rats was treated with nicotine plus the cannabinoid antagonist AM 251 and then challenged with CP 55,940. In adolescent male rats, nicotine administration led to sensitization to the locomotor-decreasing effects of both Δ9-THC and CP 55,940, but in adult male rats, the response to either drug was unchanged compared to controls. The effect of nicotine on CP 55,940-mediated locomotor activity was blocked by co-administration of AM 251 with the nicotine. Further, cannabinoid receptor density was increased in the prelimbic prefrontal cortex, ventral tegmental area, and select regions of the hippocampus in adolescent male rats pretreated with nicotine compared to vehicle-treated controls. There were no significant changes in cannabinoid receptor binding, however, in any of the brain regions examined in adult males pretreated with nicotine. The prelimbic prefrontal cortex and the hippocampus have been shown previously to be involved in stimulant reinforcement; thus it is possible that these changes contribute to the unique behavioral effects of chronic nicotine and subsequent drug administration in adolescents compared with adults. PMID

  5. Topiramate does not alter nicotine or cocaine discrimination in rats.

    PubMed

    Le Foll, Bernard; Justinova, Zuzana; Wertheim, Carrie E; Barnes, Chanel; Goldberg, Steven R

    2008-02-01

    The effects of topiramate, a potential treatment for drug dependence, were evaluated in two groups of rats trained to discriminate the administration of either 0.4 mg/kg nicotine or 10 mg/kg cocaine from that of saline, under a fixed-ratio 10 schedule of food delivery. Topiramate (1-60 mg/kg, intraperitoneal) did not produce any nicotine-like or cocaine-like discriminative effects by itself and did not produce any shift in the dose-response curves for nicotine or cocaine discrimination. Thus, the ability to discriminate the effects of nicotine or cocaine does not appear to be altered by topiramate administration. Furthermore, topiramate, given either alone or in combination with nicotine or cocaine, did not depress rates of responding. These experiments indicate that topiramate does not enhance or reduce the ability of rats to discriminate the effects of nicotine or cocaine.

  6. Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal.

    PubMed

    Watkins, S S; Koob, G F; Markou, A

    2000-02-01

    The neurobiology of nicotine addiction is reviewed within the context of neurobiological and behavioral theories postulated for other drugs of abuse. The roles of various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, gamma-aminobutyric acid, and opioid peptides in acute nicotine reinforcement and withdrawal from chronic administration are examined followed by a discussion of potential neuroadaptations within these neurochemical systems that may lead to the development of nicotine dependence. The link between nicotine administration, depression and schizophrenia are also discussed. Finally, a theoretical model of the neurobiological mechanisms underlying acute nicotine withdrawal and protracted abstinence involves alterations within dopaminergic, serotonergic, and stress systems that are hypothesized to contribute to the negative affective state associated with nicotine abstinence.

  7. 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 nic