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Sample records for underlying nicotine dependence

  1. The psychobiology of nicotine dependence

    Directory of Open Access Journals (Sweden)

    D. J. K. Balfour

    2008-12-01

    Full Text Available There is abundant evidence to show that nicotine is the principal addictive component of tobacco smoke. The results of laboratory studies have shown that nicotine has many of the behavioural and neurobiological properties of a drug of dependence. This article focuses on the evidence that nicotine has the rewarding and reinforcing properties typical of an addictive drug and that these properties are mediated, in part, by its effects on mesolimbic dopamine neurones. However, in many experimental models of dependence, nicotine has relatively weak reinforcing properties that do not appear to explain adequately the powerful addiction to tobacco smoke experienced by many habitual smokers. Some of the reasons for this conundrum will be covered herein. This article focuses on the hypothesis that sensory stimuli and other pharmacologically active components in tobacco smoke play a pivotal role in the addiction to nicotine when it is inhaled in tobacco smoke. The article will discuss the evidence that dependence upon tobacco smoke reflects a complex interaction between nicotine and the components of the smoke, which are mediated by complementary effects of nicotine on the dopamine projections to the shell and core subdivisions of the accumbens. It will also discuss the extent to which the complexity of the dependence explains why nicotine replacement therapy does not provide a completely satisfying aid to smoking cessation and speculate on the properties treatments should exhibit if they are to provide a better treatment for tobacco dependence than those currently available.

  2. Passive immunization with a nicotine-specific monoclonal antibody decreases brain nicotine levels but does not precipitate withdrawal in nicotine-dependent rats

    OpenAIRE

    Roiko, Samuel A.; Harris, Andrew C.; LeSage, Mark G.; Keyler, Daniel E.; Pentel, Paul R.

    2009-01-01

    Vaccination against nicotine is under investigation as a treatment for tobacco dependence. Passive immunization with nicotine-specific antibodies represents a complementary strategy to vaccination. A potential adverse effect of passive immunization in nicotine-dependent individuals is that it may lead to a rapid reduction in brain nicotine levels and trigger withdrawal. The goal of this study was to determine if passive immunization with the nicotine-specific monoclonal antibody Nic311 precip...

  3. Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

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    Kallupi, Marsida; George, Olivier

    2017-07-05

    Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity, and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that allows the user to simulate the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative to conventional cigarettes that emits vaporized nicotine inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner, as well as how to analyze air for nicotine content. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  4. Personality types and nicotine dependency among medical ...

    African Journals Online (AJOL)

    Personality types and nicotine dependency among medical sciences students. ... Internet Journal of Medical Update - EJOURNAL ... the students were smokers and 82.5% (330) nonsmokers; moreover, our results showed 66.7% (47) of smokers had low dependency and 33.3% (23) were physically dependent on nicotine.

  5. BEHAVIORAL MECHANISMS UNDERLYING NICOTINE REINFORCEMENT

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

    2015-01-01

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

  6. Attentional Bias in Nicotine Dependent and Non-Dependent Smokers

    OpenAIRE

    Bartlett, James

    2016-01-01

    This is a poster from the BPS Psychobiology Section Annual Scientific Meeting (2015). It explains my third year dissertation project investigating attentional bias, smoking habits, and smoking motives in nicotine dependent and non-dependent smokers.

  7. Measure nicotine dependence by the fagerström test for nicotine dependence

    OpenAIRE

    WEBER, Caroline Francieli; HATSCHBACH, Patrícia; PITHAN, Sílvia Ataide; DULLIUS, Angela Isabel dos Santos

    2017-01-01

    ABSTRACT Objective To assess the level of nicotine dependence of smokers in a university dental clinic in southern Brazil using the Fagerström Test for Nicotine Dependence and identify those who would like to quit smoking. Methods A cross-sectional study was carried out with 93 Dental School patients, who underwent a face-to-face interview with four researchers. Data was analysed using descriptive statistics and the Chi-Square test with a significance level of 5%. Results The mean age of t...

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

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

    2017-05-15

    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. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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    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

  10. Nicotine activates TRPM5-dependent and independent taste pathways.

    Science.gov (United States)

    Oliveira-Maia, Albino J; Stapleton-Kotloski, Jennifer R; Lyall, Vijay; Phan, Tam-Hao T; Mummalaneni, Shobha; Melone, Pamela; Desimone, John A; Nicolelis, Miguel A L; Simon, Sidney A

    2009-02-03

    The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5(-/-) mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products.

  11. Combination Treatment for Nicotine Dependence: State of the Science

    OpenAIRE

    INGERSOLL, KAREN S.; COHEN, JESSYE

    2005-01-01

    Both nicotine replacement and sustained-release buproprion double the odds of achieving short- and moderate-term abstinence from nicotine. However, questions remain about the efficacy of combining pharmacotherapies. Our purposes were to review the evidence for (1) combined pharmacotherapy and (2) multimodal treatment combining pharmacotherapy and behavioral treatment and to recommend combinations of treatments to reduce nicotine dependence. Combining first-line pharmacotherapies with each oth...

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

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    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.

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

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    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.

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

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    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Study of impulse control disorders among women presenting nicotine dependence.

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    Lejoyeux, Michel; Kerner, Laurent; Thauvin, Isabelle; Loi, Sabrina

    2006-01-01

    Objective. Impulse control disorders (ICDs) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania and pathological gambling. Several studies have showed an association between ICDs and alcohol use disorders. The rate of co-occurrence ICDs and nicotine dependence has never been investigated. We thus assessed the frequency of all ICDs in a population of nicotine-dependent women compared to non-smoking women. We also checked criteria of two other impulsive behaviours, compulsive buying and bulimia. Methods. Five hundred consecutive patients were assessed by a general practitioner in Paris (France). One hundred and twenty-seven women presenting the DSM-IV-R criteria for nicotine dependence were included. They were compared to 127 women consulting the same practitioner but who did not smoke. Diagnosis of ICD (pyromania, kleptomania, trichotillomania, intermittent explosive disorder, pathological gambling) and of bulimia was based on DSM-IV criteria and a modified version of the Minnesota Impulsive Disorders Interview (MIDI). Diagnosis of compulsive buying was made with the McElroy et al. criteria and a specific questionnaire. Cigarette smoking was studied using the Fagerström questionnaire and the DSM-IV-R criteria for nicotine dependence. Alcohol use disorders were assessed with the DSM-IV-R criteria for dependence and the CAGE and the MAST questionnaires. Results. Thirteen patients presented trichotillomania, 22 explosive intermittent disorder and 12 pathological gambling. All these diagnoses were equally frequent in the nicotine-positive and nicotine-negative groups. We found no case of pyromania. Compulsive buying was the most frequent impulse control disorder. It was significantly more frequent in the nicotine-positive group than in the nicotine-negative group (58 vs. 39 cases, P=0.01). Scores of the compulsive buying scale were higher in the nicotine-positive group (4.07 vs. 2.9, P=0.01). None of the patients presented an association

  16. Dependence on the nicotine gum in former smokers.

    Science.gov (United States)

    Etter, Jean-François

    2009-03-01

    We conducted an Internet survey in 2004-2007 in 526 daily users of the nicotine gum, to assess use of, and dependence on the nicotine gum in former smokers. We used modified versions of the Nicotine Dependence Syndrome Scale (NDSS-G), the Cigarette Dependence Scale (CDS-G) and the Fagerström Test (FTND-G). After 30 days, 155 participants (29%) indicated their gum use. Higher dependence on the gum predicted a lower chance of stopping using it at follow-up (odds ratio=0.36 for each standard deviation unit on CDS-G, p=0.001). More long-term (>3 months) than short-term (dependence on the gum than short-term users, as assessed with NDSS-Gum, CDS-Gum and FTND-Gum (all pdependence on the nicotine gum. Lower levels of dependence on the gum predicted cessation of gum use. However, long term use of the nicotine gum has no known serious adverse consequence, and may be beneficial if it prevents late relapse.

  17. Smoking cigarettes of low nicotine yield does not reduce nicotine intake as expected: a study of nicotine dependency in Japanese males

    Directory of Open Access Journals (Sweden)

    Ozasa Kotaro

    2004-07-01

    Full Text Available Abstract Background Many Japanese believe that low-yield cigarettes are less hazardous than regular cigarettes, and many smokers consume low-yield cigarettes to reduce their risks from smoking. We evaluate the association between actual nicotine intake and brand nicotine yield, and the influence of nicotine dependence on this association. Methods The study subjects included 458 Japanese male smokers, aged 51.2 ± 9.9 years, who participated in health check-ups in a hospital in 1998 and 2000. Each subject filled out a self-administered smoking questionnaire and the score of each on the Fagerström Test for Nicotine Dependence was calculated. Urinary cotinine concentration was measured at the time of participation. Results The geometric mean of urinary cotinine concentration was 535 ng/mgCr for those who smoked brands with the lowest nicotine (0.1 mg on the package, compared with 1010 ng/mgCr for those who smoked brands with the highest (0.9–2.4 mg, weighted mean of 1.1 mg. Thus, despite the 11-fold ratio of nicotine yield on the packages, the ratio of urinary cotinine level was less than twofold. Both nicotine yield on the package and nicotine dependence significantly increased urinary cotinine concentration, and the negative interaction between them almost attained statistical significance. Cotinine concentration in heavily dependent smokers was consistently high regardless of the nicotine yield of brands. Conclusions The nicotine yield of cigarettes measured by machine-smoking does not reliably predict the exposure of smokers. Smokers consuming low-yield nicotine cigarettes did not reduce actual intake of nicotine to the level that might be expected, especially for those heavily dependent on nicotine. Current labeling practices are misleading for the two-third of smokers who are moderately or highly dependent on nicotine.

  18. Cue dependency of nicotine self-administration and smoking.

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    Caggiula, A R; Donny, E C; White, A R; Chaudhri, N; Booth, S; Gharib, M A; Hoffman, A; Perkins, K A; Sved, A F

    2001-12-01

    A paradox exists regarding the reinforcing properties of nicotine. The abuse liability associated with smoking equals or exceeds that of other addictive drugs, yet the euphoric, reinforcing and other psychological effects of nicotine, compared to these other drugs, are more subtle, are manifest under more restricted conditions, and do not readily predict the difficulty most smokers experience in achieving abstinence. One possible resolution to this apparent inconsistency is that environmental cues associated with drug delivery become conditioned reinforcers and take on powerful incentive properties that are critically important for sustaining smoking in humans and nicotine self-administration in animals. We tested this hypothesis by using a widely employed self-administration paradigm in which rats press a lever at high rates for 1 h/day to obtain intravenous infusions of nicotine that are paired with two types of visual stimuli: a chamber light that when turned on signals drug availability and a 1-s cue light that signals drug delivery. We show that these visual cues are at least as important as nicotine in sustaining a high rate of responding once self-administration has been established, in the degree to which withdrawing nicotine extinguishes the behavior, and in the reinstatement of lever pressing after extinction. Additional studies demonstrated that the importance of these cues was manifest under both fixed ratio and progressive ratio (PR) schedules of reinforcement. The possibility that nicotine-paired cues are as important as nicotine in smoking behavior should refocus our attention on the psychology and neurobiology of conditioned reinforcers in order to stimulate the development of more effective treatment programs for smoking cessation.

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

    Directory of Open Access Journals (Sweden)

    Kia J Jackson

    Full Text Available 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.

  20. The relationship of childhood trauma to nicotine dependence in pregnant smokers.

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    Blalock, Janice A; Nayak, Nisha; Wetter, David W; Schreindorfer, Lisa; Minnix, Jennifer A; Canul, Jennifer; Cinciripini, Paul M

    2011-12-01

    Pregnant women with high levels of nicotine dependence are the least likely to quit smoking spontaneously during pregnancy or to benefit from smoking cessation interventions. In the general population, there is increasing evidence of a relationship between smoking, nicotine dependence, and exposure to childhood trauma. We examined the relationship of childhood trauma to several measures of nicotine dependence and evaluated whether this relationship was mediated by major depressive disorder or depressive symptom severity in pregnant smokers. Moderate to extreme levels of childhood trauma were significantly related to smoking within 5 minutes or less of waking, and to the Behavioral Choice-Melioration, Negative Reinforcement, and Tolerance subscales of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) scale. The relationships between childhood emotional abuse and the WISDM-68 Total and Negative Reinforcement subscale were partially mediated by depressive symptoms. Results suggest that childhood trauma may be a risk factor underlying nicotine dependence in pregnant smokers. Increased understanding of the relationship of affect regulation to smoking in individuals with childhood trauma histories may aid in the development of more effective treatments of nicotine dependence for this population of smokers.

  1. Effects of Nicotine Dependence and Depressive Symptoms on Smoking Cessation: A Longitudinal Study Among Adolescents

    NARCIS (Netherlands)

    Scherphof, C.S.; Eijnden, R.J.J.M. van den; Harakeh, Z.; Raaijmakers, Q.A.W.; Kleinjan, M.; Engels, R.C.M.E.; Vollebergh, W.A.M.

    2013-01-01

    Nicotine dependence has been shown to hamper successful smoking cessation in adolescents. Nicotine dependence and depression are highly comorbid, but the relation between depression and smoking cessation is not yet fully understood. Therefore, the present study examines both the longitudinal

  2. Analyzing the pathways enriched in genes associated with nicotine dependence in the context of human protein-protein interaction network.

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    Hu, Ying; Fang, Zhonghai; Yang, Yichen; Fan, Ting; Wang, Ju

    2018-03-16

    Nicotine dependence is the primary addictive stage of cigarette smoking. Although a lot of studies have been performed to explore the molecular mechanism underlying nicotine dependence, our understanding on this disorder is still far from complete. Over the past decades, an increasing number of candidate genes involved in nicotine dependence have been identified by different technical approaches, including the genetic association analysis. In this study, we performed a comprehensive collection of candidate genes reported to be genetically associated with nicotine dependence. Then, the biochemical pathways enriched in these genes were identified by considering the gene's propensity to be related to nicotine dependence. One of the most widely used pathway enrichment analysis approach, over-representation analysis, ignores the function non-equivalence of genes in candidate gene set and may have low discriminative power in identifying some dysfunctional pathways. To overcome such drawbacks, we constructed a comprehensive human protein-protein interaction network, and then assigned a function weighting score to each candidate gene based on their network topological features. Evaluation indicated the function weighting score scheme was consistent with available evidence. Finally, the function weighting scores of the candidate genes were incorporated into pathway analysis to identify the dysfunctional pathways involved in nicotine dependence, and the interactions between pathways was detected by pathway crosstalk analysis. Compared to conventional over-representation based pathway analysis tool, the modified method exhibited improved discriminative power and detected some novel pathways potentially underlying nicotine dependence. In summary, we conducted a comprehensive collection of genes associated with nicotine dependence and then detected the biochemical pathways enriched in these genes using a modified pathway enrichment analysis approach with function weighting

  3. Combination treatment for nicotine dependence: state of the science.

    Science.gov (United States)

    Ingersoll, Karen S; Cohen, Jessye

    2005-01-01

    Both nicotine replacement and sustained-release buproprion double the odds of achieving short- and moderate-term abstinence from nicotine. However, questions remain about the efficacy of combining pharmacotherapies. Our purposes were to review the evidence for (1) combined pharmacotherapy and (2) multimodal treatment combining pharmacotherapy and behavioral treatment and to recommend combinations of treatments to reduce nicotine dependence. Combining first-line pharmacotherapies with each other or with investigational drugs shows little benefit. In contrast, trials combining specific behavioral treatments with first-line pharmacotherapies show enhanced smoking cessation rates, but benefits are not seen in all populations. We recommend future directions for research, including better specification of behavioral components and further examination of the length and timing of treatment.

  4. Genetics of addictive behavior: the example of nicotine dependence.

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    Gorwood, Philip; Le Strat, Yann; Ramoz, Nicolas

    2017-09-01

    The majority of addictive disorders have a significant heritability-roughly around 50%. Surprisingly, the most convincing association (a nicotinic acetylcholine receptor CHRNA5-A3-B4 gene cluster in nicotine dependence), with a unique attributable risk of 14%, was detected through a genome-wide association study (GWAS) on lung cancer, although lung cancer has a low heritability. We propose some explanations of this finding, potentially helping to understand how a GWAS strategy can be successful. Many endophenotypes were also assessed as potentially modulating the effect of nicotine, indirectly facilitating the development of nicotine dependence. Challenging the involved phenotype led to the demonstration that other potentially overlapping disorders, such as schizophrenia and Parkinson disease, could also be involved, and further modulated by parent monitoring or the existence of a smoking partner. Such a complex mechanism of action is compatible with a gene-environment interaction, most clearly explained by epigenetic factors, especially as such factors were shown to be, at least partly, genetically driven.

  5. Personality types and nicotine Dependency among medical sciences students

    Directory of Open Access Journals (Sweden)

    H. Bakshi

    2014-01-01

    Full Text Available Smoking has recently become a major public health threat among the youth of today in Iran. Many clinicians and researchers hypothesized that tobacco-related disorders are maintained by the ability of nicotine to regulate positive and negative mood states. Moreover, some research indicates that there is no correlation between personality type, cigarette smoking, and heart disease, while some others mention that people with personality type A are more inclined towards smoking and related diseases. Thus, to test this hypothesis, we have studied possible correlations between psychological personality and tobacco-dependency among university students in the central part of Iran. In the current study, the most prevalent personality type was B (56.8%, with A (43.2%. Regarding smoking status, 17.5% (70 of the students were smokers and 82.5% (330 non-smokers; moreover, our results showed 66.7% (47 of smokers had low dependency and 33.3% (23 were physically dependent on nicotine. Concerning the difference between smokers and non-smokers based on their personality type, the results showed that 51.4% smokers had type A personality and 59.9% non-smokers were type B. There were also statistical differences between personality type and tobacco usage in students (p<0.05. We also found statistical differences between physical dependency and personality type; that is, 67.3% of smoking students who were physically dependent on nicotine had A type personality (p<0.05. The results suggest that there are several psychological types having higher association with tobacco use than other types. It poses some additional challenges for students’ support services to address mental health problems. The personality type in our study turned out to be an important factor influencing the nicotine dependency of the students.

  6. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.

    Science.gov (United States)

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

    2008-12-01

    A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.

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

    OpenAIRE

    Kenney, Justin W.; Gould, Thomas J.

    2008-01-01

    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 ...

  8. Preliminary test of cigarette nicotine discrimination threshold in non-dependent versus dependent smokers.

    Science.gov (United States)

    Perkins, Kenneth A; Kunkle, Nicole; Karelitz, Joshua L; Perkins, K A; Kunkle, N; Karelitz, J L

    2017-06-01

    Despite its potential for understanding tobacco dependence, behavioral discrimination of nicotine via smoking has not been formally examined as a function of nicotine dependence level. Spectrum research cigarettes were used to compare non-dependent with dependent smokers on the lowest content of nicotine they could discriminate (i.e., "threshold"). Dependent (n=21; 16M, 5F) or non-dependent (n=7; 4M, 3F) smokers were tested on ability to discriminate between cigarettes with nicotine contents of 17, 11, 5, 2, and 1mg/g, one per session, from an "ultra-low" cigarette with 0.4mg/g (all had 9-10mg "tar"). All abstained from smoking overnight prior to sessions, and number of sessions was determined by the lowest nicotine content they could reliably discriminate from the ultra-low on >80% of trials (i.e., ≥5 of 6). Subjective perceptions and cigarette choice behavior were also assessed and related to discrimination behavior. Discrimination thresholds (and most perceptions) did not differ between dependent and non-dependent smokers, with median thresholds of 11mg/g for both subgroups. Yet, "liking" and puff choice for threshold cigarettes were greater in dependent but not non-dependent smokers, while cigarettes with nicotine contents below threshold did not support "liking" or choice in both groups. In sum, this preliminary study suggests threshold for discriminating nicotine via smoking may not vary by dependence level, and further study is needed to confirm that cigarettes unable to be discriminated are also not reinforcing. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    Science.gov (United States)

    Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen

    2013-01-01

    The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction. PMID:21822688

  10. Lack of reinforcement enhancing effects of nicotine in non-dependent smokers.

    Science.gov (United States)

    Perkins, Kenneth A; Grottenthaler, Amy; Wilson, Annette S

    2009-09-01

    Recent animal research has shown that, aside from its primary and secondary reinforcing effects, nicotine may enhance reinforcement from stimuli unrelated to nicotine intake. Little human research has directly examined this potentially important influence of nicotine. We report two virtually identical studies examining the influence of nicotine, via nasal spray (study 1) and cigarettes (study 2), on the reinforcing effects of rewards unrelated to nicotine intake. Both studies involved young adults with some past smoking exposure but no history of nicotine dependence. Reinforcement was assessed by responses on a simple operant computer task reinforced by: money, music, the termination of aversive noise, or no reward (control). Participants responded for rewards on three separate sessions, involving intermittent dosing of 0, 5, or 10 microg/kg nicotine via nasal spray (study 1) or the smoking of 0.05 or 0.6 mg nicotine cigarettes or no smoking (study 2). Results showed no effects of nicotine, by nasal spray or cigarette smoking, on reinforced responses, although nicotine increased some subjective responses (e.g. head rush/buzzed, liking). Nicotine via smoking also did not influence affect or hedonic ratings of slides varying in mood valence in an exploratory trial in study 2. These results do not support the notion that nicotine per se enhances the reinforcing value of other reinforcers in humans. Any reinforcement enhancing effects of nicotine in humans may be specific to dependent smokers or may be relatively narrow and dependent upon procedural conditions different from those in the current studies.

  11. Neuronal Nicotinic Acetylcholine Receptors: Neuroplastic Changes underlying Alcohol and Nicotine Addictions

    Directory of Open Access Journals (Sweden)

    Allison Anne Feduccia

    2012-08-01

    Full Text Available Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug’s reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs. The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine’s effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.

  12. Decision-making style, nicotine and caffeine use and dependence.

    Science.gov (United States)

    Phillips, James G; Ogeil, Rowan P

    2015-11-01

    As therapeutic interventions are being developed utilising telehealth and mobile phones, it is important to understand how substance-dependent individuals will respond to offers of online assistance. The present paper considered the following: (1) how decision-making style is associated with use and dependence upon commonly used stimulants and (2) how it influences behavioural responses to electronic offers of further information about these drugs. An online survey examined patterns of nicotine and caffeine use, administered Severity of Dependence Scales for caffeine and nicotine and assessed decision-making style using the Melbourne Decision Making Questionnaire and mood using the Kessler Distress Scale. Upon completing these scales, the 181 participants with a mean age of 28.14 years were offered further information online. Stimulant dependence was associated with psychological distress. Caffeine dependence was linked to hypervigilance (panic). Decisional self-esteem varied with stimulant dependence and Kessler Distress Scale score. Participants with high decisional self-esteem declined electronic offers of further information. Confidence rather than defensive avoidance was a factor in reducing information-seeking behaviours on the Internet. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Zuo Jun Ren

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  16. Predictive model of nicotine dependence based on mental health indicators and self-concept

    Directory of Open Access Journals (Sweden)

    Hamid Kazemi Zahrani

    2014-12-01

    Full Text Available Background: The purpose of this research was to investigate the predictive power of anxiety, depression, stress and self-concept dimensions (Mental ability, job efficiency, physical attractiveness, social skills, and deficiencies and merits as predictors of nicotine dependency among university students in Isfahan. Methods: In this correlational study, 110 male nicotine-dependent students at Isfahan University were selected by convenience sampling. All samples were assessed by Depression Anxiety Stress Scale (DASS, self-concept test and Nicotine Dependence Syndrome Scale. Data were analyzed by Pearson correlation and stepwise regression. Results: The result showed that anxiety had the highest strength to predict nicotine dependence. In addition, the self-concept and its dimensions predicted only 12% of the variance in nicotine dependence, which was not significant. Conclusion: Emotional processing variables involved in mental health play an important role in presenting a model to predict students’ dependence on nicotine more than identity variables such as different dimensions of self-concept.

  17. Chronic nicotine pretreatment is sufficient to upregulate α4* nicotinic receptors and increase oral nicotine self-administration in mice

    OpenAIRE

    Renda, Anthony; Nashmi, Raad

    2014-01-01

    Background Understanding the underlying causes of nicotine addiction will require a multidisciplinary approach examining the key molecular, cellular and neuronal circuit functional changes that drive escalating levels of nicotine self-administration. In this study, we examined whether mice pretreated with chronic nicotine, at a dosing regimen that results in maximal nicotinic acetylcholine receptor (nAChR) upregulation, would display evidence of nicotine-dependent behaviour during nicotine se...

  18. Use of High-Nicotine/Tar-Yield (Full-Flavor) Cigarettes and Risk for Nicotine Dependence in Nationally Representative Samples of US Smokers.

    Science.gov (United States)

    Redner, Ryan; White, Thomas J; Bunn, Janice Y; Higgins, Stephen T

    2016-06-01

    The present study examines whether use of machine-estimated high-nicotine/tar-yield (full-flavor) cigarettes predicts greater risk of nicotine dependence after controlling for the influence of potential confounding factors in US nationally representative samples. Data were obtained from multiple years of the National Survey on Drug Use and Health (NSDUH). Nicotine dependence was measured by (1) the Nicotine Dependence Syndrome Scale and (2) latency to first cigarette after waking. Associations between use of high-nicotine/tar-yield cigarettes and risk for nicotine dependence were examined using multiple logistic regression. The odds of nicotine dependence were reliably greater among users of high- compared to lower-nicotine/tar-yield cigarettes even after adjusting for sociodemographic and other smoking characteristics (Ps marketing and availability of high-nicotine/tar-yield cigarettes is increasing risk of nicotine dependence among US smokers warrants further research. This study adds additional empirical evidence to the relation of machine measured high-yield cigarettes and likelihood of nicotine dependence, and draws some implications in regards to regulation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. The Relationship of Childhood Trauma to Nicotine Dependence in Pregnant Smokers

    OpenAIRE

    Blalock, Janice A.; Nayak, Nisha; Wetter, David W.; Schreindorfer, Lisa; Minnix, Jennifer A.; Canul, Jennifer; Cinciripini, Paul M.

    2011-01-01

    Pregnant women with high levels of nicotine dependence are the least likely to quit smoking spontaneously during pregnancy or to benefit from smoking cessation interventions. In the general population, there is increasing evidence of a relationship between smoking, nicotine dependence, and exposure to childhood trauma. We examined the relationship of childhood trauma to several measures of nicotine dependence and evaluated whether this relationship was mediated by major depressive disorder or...

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

    Science.gov (United States)

    Etter, Jean-François; Eissenberg, Thomas

    2015-02-01

    To assess dependence levels in users of e-cigarettes, and compare them with dependence levels in users of nicotine gums and tobacco cigarettes. Self-reports from cross-sectional Internet and mail surveys. Comparisons of: (a) 766 daily users of nicotine-containing e-cigarettes with 30 daily users of nicotine-free e-cigarettes; (b) 911 former smokers who used the e-cigarette daily with 451 former smokers who used the nicotine gum daily (but no e-cigarette); (c) 125 daily e-cigarette users who smoked daily (dual users) with two samples of daily smokers who did not use e-cigarettes (2206 enrolled on the Internet and 292 enrolled by mail from the general population of Geneva). We used the Fagerström test for nicotine dependence, the nicotine dependence syndrome scale, the cigarette dependence scale and versions of these scales adapted for e-cigarettes and nicotine gums. Dependence ratings were slightly higher in users of nicotine-containing e-cigarettes than in users of nicotine-free e-cigarettes. In former smokers, long-term (>3 months) users of e-cigarettes were less dependent on e-cigarettes than long-term users of the nicotine gum were dependent on the gum. There were few differences in dependence ratings between short-term (≤3 months) users of gums or e-cigarettes. Dependence on e-cigarettes was generally lower in dual users than dependence on tobacco cigarettes in the two other samples of daily smokers. Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Role of nicotine dependence on the relationship between variants in the nicotinic receptor genes and risk of lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Tung-Sung Tseng

    Full Text Available Several variations in the nicotinic receptor genes have been identified to be associated with both lung cancer risk and smoking in the genome-wide association (GWA studies. However, the relationships among these three factors (genetic variants, nicotine dependence, and lung cancer remain unclear. In an attempt to elucidate these relationships, we applied mediation analysis to quantify the impact of nicotine dependence on the association between the nicotinic receptor genetic variants and lung adenocarcinoma risk. We evaluated 23 single nucleotide polymorphisms (SNPs in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4 previously reported to be associated with lung cancer risk and smoking behavior and 14 SNPs in the four 'control' genes (TERT, CLPTM1L, CYP1A1, and TP53, which were not reported in the smoking GWA studies. A total of 661 lung adenocarcinoma cases and 1,347 controls with a smoking history, obtained from the Environment and Genetics in Lung Cancer Etiology case-control study, were included in the study. Results show that nicotine dependence is a mediator of the association between lung adenocarcinoma and gene variations in the regions of CHRNA5/A3/B4 and accounts for approximately 15% of this relationship. The top two CHRNA3 SNPs associated with the risk for lung adenocarcinoma were rs1051730 and rs12914385 (p-value = 1.9×10(-10 and 1.1×10(-10, respectively. Also, these two SNPs had significant indirect effects on lung adenocarcinoma risk through nicotine dependence (p = 0.003 and 0.007. Gene variations rs2736100 and rs2853676 in TERT and rs401681 and rs31489 in CLPTM1L had significant direct associations on lung adenocarcinoma without indirect effects through nicotine dependence. Our findings suggest that nicotine dependence plays an important role between genetic variants in the CHRNA5/A3/B4 region, especially CHRNA3, and lung adenocarcinoma. This may provide valuable information for

  2. The Effect of Nicotine Dependence on Psychopathology in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Anne Yee

    2015-01-01

    Full Text Available Introduction. Our study aims to determine the prevalence of nicotine dependence and investigate the effect of nicotine dependence on psychopathology among schizophrenia patients. Methods. A cross-sectional study was carried out in an outpatient psychiatric clinic at a general hospital in Malaysia. 180 recruited subjects were administered the Malay version of Mini International Neuropsychiatric Interview (MINI, the Positive and Negative Symptom Scale (PANSS, and the Malay version of Fagerstrom Test for Nicotine Dependence (FTND-M questionnaires. Results. The prevalence of nicotine dependence among the subjects was 38.1% (n=69 and they were mainly composed of male gender, Malay ethnicity, being treated with atypical antipsychotics, and taking other illicit drugs or alcohol. Subjects with severe nicotine dependence scored less in the negative subscale of PANSS compared with the nonsmokers (P=0.011. On performing the hierarchy multiple regressions, dependence status still significantly predicted negative scores after adjusting the confounders (t=-2.87, P=0.005. Conclusion. The rate of nicotine use disorder among schizophrenia patients in this study is higher than that of the general population in Malaysia. The significant association between nicotine dependence and negative psychopathology symptoms will help the healthcare practitioners in their management of nicotine dependence among schizophrenia patients.

  3. The influence of occupational stress factors on the nicotine dependence: a cross sectional study

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    Wolf Jürgen

    2010-04-01

    Full Text Available Abstract Objective This study analyses the association between occupational stress factors and nicotine dependence. Our hypothesis is that occupational stress factors increase nicotine dependence. Methods Data were taken from the Cologne Smoking Study, a case-control study that examines which genetic/psychosocial factors lead to a higher risk for smokers to suffer from cardiac infarction, lung cancer and/or to become addicted to nicotine. Our sample consisted of N = 197 currently smoking and employed participants. Nicotine dependence was measured using the Fagerström Test for Nicotine Dependence (FTND. The extent of the stress factors experienced at work was assessed using the Effort-Reward Imbalance scale (ERI. Logistic regression was used for the statistical analysis. Results Contrary to our hypothesis, the results show that occupational stress factors are actually associated with lower levels of nicotine dependence (N = 197; adjusted OR = 0.439; p = .059. Conclusions One possible explanation for the study's findings is that the participants have a heavy workload and can only smoke in their spare time. Another reason may be workplace smoking bans. Furthermore, the Fagerström Test for Nicotine Dependence is unable to examine nicotine dependence during working hours.

  4. In alcohol-dependent drinkers, what does the presence of nicotine dependence tell us about psychiatric and addictive disorders comorbidity?

    Science.gov (United States)

    Le Strat, Yann; Ramoz, Nicolas; Gorwood, Philip

    2010-01-01

    To examine the pattern of psychiatric comorbidity associated with nicotine dependence among alcohol-dependent respondents in the general population. Drawn from a US national survey of 43,000 adults The (National Epidemiologic Survey on Alcohol and Related Conditions) who took part in a face-to-face interview, data were examined on the 4782 subjects with lifetime alcohol dependence, and comparisons were made between those with and those without nicotine dependence. Nicotine dependence was reported by 48% of the alcohol-dependent respondents. They reported higher lifetime rates of panic disorder, specific and social phobia, generalized anxiety disorder, major depressive episode, manic disorder, suicide attempt, antisocial personality disorder and all addictive disorders than those without nicotine dependence. After controlling for the effects of any psychiatric and addictive disorder, alcohol-dependent subjects with nicotine dependence were more than twice as likely as non-nicotine-dependent, alcohol-dependent subjects to have at least one other lifetime addiction diagnosis (adjusted odds ratio 2.36; 95% confidence interval 2.07-2.68). Nicotine dependence represents a general marker of psychiatric comorbidity, particularly of addictive comorbidity. It may be used as a screening measure for psychiatric diagnoses in clinical practice as well as in future trials.

  5. Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    OpenAIRE

    Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen; Gould, Thomas J.

    2011-01-01

    The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute ...

  6. Smoking practices and nicotine dependence among adolescents in Pakistan

    International Nuclear Information System (INIS)

    Sami, N.

    2013-01-01

    Objective: To find out the smoking prevalence and associated factors among in-school and out-of-school adolescents and their nicotine dependence. Method: The cross-sectional study was conducted from April to June 2008 comprising 1014 adolescents aged 12-18 years residing in two rural districts of Sindh and Punjab. Trained interviewers collected information from the adolescents regarding age, ethnicity, religion, occupation and education of parents, smoking behaviour, smoking history of family/friend, type of family system, number of siblings and place of residence. Statistical package Epi-Info version 6 was used to enter the data and analysis was performed by using SPSS version 12. Results: Overall smoking prevalence among the 1014 adolescents was 15.2%, with significant gender stratification (7.9% among girls versus 20.2% among boys). Of these, 50% were moderately nicotine dependent. However, the prevalence among in-school adolescents (14.6%) was not significantly different from out-of-school adolescents (16.1%). The factors associated with adolescents smoking were father's illiteracy (adjusted odds ratio [OR]= 8.2), friend's smoking (adjusted OR=6.8), father's smoking (adjusted OR=5.4) and nuclear family setup (adjusted OR=3.6). When explored for the first place of smoking, friend's home was mentioned by majority of adolescents boys and girls. Conclusion: Although there was a significant difference found between the prevalence of smoking among adolescent males and females, but any difference among in-school and out-of-school adolescents smoking prevalence could not be established. (author)

  7. Factorial and convergent validity of nicotine dependence measures in adolescents: Towards a multidimensional approach

    NARCIS (Netherlands)

    Kleinjan, M.; Eijnden, R.J.J.M. van den; Leeuwe, J.F.J. van; Otten, R.; Brug, J.; Engels, R.C.M.E.

    2007-01-01

    The present study investigated the possibility of forming a multidimensional scale for the measurement of nicotine dependence among adolescents, based on the modified Fagerstrom Tolerance Questionnaire (mFTQ) and the Hooked on Nicotine Checklist (HONC). A survey was conducted among 33 Dutch

  8. Activation of nicotinic receptors can contribute to endothelium-dependent relaxations to acetylcholine in the rat aorta.

    Science.gov (United States)

    Zou, Qian; Leung, Susan W S; Vanhoutte, Paul M

    2012-06-01

    Acetylcholine causes endothelium-dependent relaxations in the rat aorta. Both muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs) are expressed in endothelial cells. It is generally accepted that mAChRs are responsible for the endothelium-dependent relaxations evoked by acetylcholine. The present study was designed to investigate whether nAChRs can also be involved in such responses evoked by the cholinergic transmitter. Rings with or without endothelium of aortae of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats were suspended in organ chambers for the measurement of isometric tension. In WKY aortae the muscarinic antagonist atropine abolished the relaxations to increasing concentrations of acetylcholine, confirming that mAChRs are responsible mainly for the response under control conditions. In SHR aortae, atropine caused only partial inhibition of the endothelium-dependent relaxations to acetylcholine; the remaining decreases in tension were inhibited by the nicotinic antagonist mecamylamine, which did not significantly affect the response in the absence of atropine in either SHR or WKY preparations. Thus, when mAChRs are inhibited, nAChRs mediate relaxation to the cholinergic transmitter in the SHR but not the WKY aorta. Nicotine, a direct agonist of the nicotinic receptor, induced endothelium-dependent relaxations in both SHR and WKY rats via the activation of α7-nAChRs, but not by mecamylamine-sensitive nicotinic receptors (α3 subtype). The acetylcholine-induced, atropine-insensitive relaxations and those to nicotine both involve the phosphatidylinositol 3-kinase/AKT pathway. The present study demonstrates that the activation of nAChRs can contribute to acetylcholine-induced, endothelium-dependent relaxations in the aortae of hypertensive animals and suggests that these receptors may contribute to the endothelium-dependent regulation of vascular tone.

  9. Exploring the Severity of Dependence Scale (SDS) as a possible measure of nicotine dependence.

    Science.gov (United States)

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

    2016-01-01

    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. 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. 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., cigarettes per day [CPD], carbon monoxide [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. Findings suggest that SDS and TTFC assess different constructs of nicotine dependence; among smokers, the SDS appears to tap into nonphysical 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 3 SDS items in addition to TTFC may offer utility over using TTFC alone.

  10. Tobacco use and nicotine dependence among conflict-affected men in the Republic of Georgia.

    Science.gov (United States)

    Roberts, Bayard; Chikovani, Ivdity; Makhashvili, Nino; Patel, Vikram; McKee, Martin

    2013-05-29

    There is very little evidence globally on tobacco use and nicotine dependence among civilian populations affected by armed conflict, despite key vulnerability factors related to elevated mental disorders and socio-economic stressors. The study aim was to describe patterns of smoking and nicotine dependence among conflict-affected civilian men in the Republic of Georgia and associations with mental disorders. A cross-sectional household survey using multistage random sampling was conducted in late 2011 among conflict-affected populations in Georgia. Respondents included in this paper were 1,248 men aged ≥18 years who were internally displaced persons (IDPs) and former IDPs who had returned in their home areas. Outcomes of current tobacco use, heavy use (≥20 cigarettes per day), and nicotine dependence (using the Fagerström Test for Nicotine Dependence) were used. PTSD, depression, anxiety and hazardous alcohol use were also measured, along with exposure to traumatic events and a range of demographic and socio-economic characteristics. Of 1,248 men, 592 (47.4%) smoked and 70.9% of current smokers were heavy smokers. The mean nicotine dependence score was 5.0 and the proportion with high nicotine dependence (≥6) was 41.4%. In multivariate regression analyses, nicotine dependence was significantly associated with PTSD (β 0.74) and depression (β 0.85), along with older age (except 65+ years), and being a returnee (compared to IDPs). The study reveals very high levels of heavy smoking and nicotine dependence among conflict-affected persons in Georgia. The associations between nicotine dependence, PTSD and depression suggest interventions could yield synergistic benefits.

  11. Tobacco Use and Nicotine Dependence among Conflict-Affected Men in the Republic of Georgia

    Directory of Open Access Journals (Sweden)

    Vikram Patel

    2013-05-01

    Full Text Available Background: There is very little evidence globally on tobacco use and nicotine dependence among civilian populations affected by armed conflict, despite key vulnerability factors related to elevated mental disorders and socio-economic stressors. The study aim was to describe patterns of smoking and nicotine dependence among conflict-affected civilian men in the Republic of Georgia and associations with mental disorders. Methods: A cross-sectional household survey using multistage random sampling was conducted in late 2011 among conflict-affected populations in Georgia. Respondents included in this paper were 1,248 men aged ≥18 years who were internally displaced persons (IDPs and former IDPs who had returned in their home areas. Outcomes of current tobacco use, heavy use (≥20 cigarettes per day, and nicotine dependence (using the Fagerström Test for Nicotine Dependence were used. PTSD, depression, anxiety and hazardous alcohol use were also measured, along with exposure to traumatic events and a range of demographic and socio-economic characteristics. Results: Of 1,248 men, 592 (47.4% smoked and 70.9% of current smokers were heavy smokers. The mean nicotine dependence score was 5.0 and the proportion with high nicotine dependence (≥6 was 41.4%. In multivariate regression analyses, nicotine dependence was significantly associated with PTSD (β 0.74 and depression (β 0.85, along with older age (except 65+ years, and being a returnee (compared to IDPs. Conclusions: The study reveals very high levels of heavy smoking and nicotine dependence among conflict-affected persons in Georgia. The associations between nicotine dependence, PTSD and depression suggest interventions could yield synergistic benefits.

  12. Physical activity moderates the association between nicotine dependence and depression among U.S. smokers.

    Science.gov (United States)

    Loprinzi, Paul D; Walker, Jerome F; Kane, Christy; Cardinal, Bradley J

    2014-01-01

    Research demonstrates that nicotine dependence and depression are associated and that physical activity is effective in reducing depression symptoms. However, our understanding of the potential beneficial effects of physical activity on depression in current smokers is more limited. The purpose of this study was to examine whether physical activity moderates the association between nicotine dependence and depression in U.S. smokers. Cross-sectional. National Health and Nutrition Examination Survey 2005-2006. Four hundred forty-one current adult smokers. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess nicotine dependence and depression. Effect modification and statistical interaction models were used. Both models were significant. With regard to the statistical interaction model, and after controlling for age, gender, race/ethnicity, education, comorbidity index, homocysteine, cotinine, total cholesterol, sedentary behavior, and vitamins C, D, and E, objectively measured physical activity moderated the association between nicotine dependence and depression (interaction variable: odds ratio = 3.43; 95% confidence interval: 1.02-11.51; p = .04). In this national sample of current smokers, physical activity moderated the association between nicotine dependence and depression. These results suggest that those individuals with nicotine dependence and who are less physically active are more likely to be depressed than what would be expected on the basis of the individual effects of nicotine and physical inactivity separately.

  13. Greater elevation in risk for nicotine dependence per pack of cigarettes smoked among those with an anxiety disorder.

    Science.gov (United States)

    Kushner, Matt G; Menary, Kyle R; Maurer, Eric W; Thuras, Paul

    2012-11-01

    Recent work shows that the time from the initial use of nicotine, cannabis, and alcohol to the onset of dependence on these substances is shorter ("telescoped") in anxiety-disordered individuals. Previously, we hypothesized that telescoping may result from a shared neurobiology underlying both anxiety disorders and dependence. This hypothesis implies that telescoping occurs because individuals with an anxiety disorder transition to dependence with less overall drug exposure ("dependence susceptibility"). To investigate this further, we examined an estimate of the amount smoked (rather than the time transpired) from smoking initiation milestones to the onset of nicotine dependence in those with and without an anxiety disorder. We used the subset of respondents in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 1 who reported having smoked at least 100 cigarettes (N = 18,013). All data were based on face-to-face interviews. Individuals with any anxiety disorder transitioned to nicotine dependence after smoking fewer total cigarettes than did individuals with no anxiety disorder. Furthermore, those with more than one anxiety disorder transitioned to nicotine dependence after smoking fewer cigarettes than did those with one anxiety disorder only. Several potentially confounding covariates were controlled for in these analyses. Dependence susceptibility is a novel concept with the potential to inform theoretical accounts of and prevention strategies for substance dependence among those with an anxiety disorder. In addition to nicotine, our theory and past data suggest that dependence susceptibility for other addictive substances (e.g., alcohol) also would be found among those with an anxiety disorder.

  14. Nicotine dependence, "background" and cue-induced craving and smoking in the laboratory.

    Science.gov (United States)

    Dunbar, Michael S; Shiffman, Saul; Kirchner, Thomas R; Tindle, Hilary A; Scholl, Sarah M

    2014-09-01

    Nicotine dependence has been associated with higher "background" craving and smoking, independent of situational cues. Due in part to conceptual and methodological differences across past studies, the relationship between dependence and cue-reactivity (CR; e.g., cue-induced craving and smoking) remains unclear. 207 daily smokers completed six pictorial CR sessions (smoking, negative affect, positive affect, alcohol, smoking prohibitions, and neutral). Individuals rated craving before (background craving) and after cues, and could smoke following cue exposure. Session videos were coded to assess smoking. Participants completed four nicotine dependence measures. Regression models assessed the relationship of dependence to cue-independent (i.e., pre-cue) and cue-specific (i.e., pre-post cue change for each cue, relative to neutral) craving and smoking (likelihood of smoking, latency to smoke, puff count). Dependence was associated with background craving and smoking, but did not predict change in craving across the entire sample for any cue. Among alcohol drinkers, dependence was associated with greater increases in craving following the alcohol cue. Only one dependence measure (Wisconsin Inventory of Smoking Dependence Motives) was consistently associated with smoking reactivity (higher likelihood of smoking, shorter latency to smoke, greater puff count) in response to cues. While related to cue-independent background craving and smoking, dependence is not strongly associated with laboratory cue-induced craving under conditions of minimal deprivation. Dependence measures that incorporate situational influences on smoking correlate with greater cue-provoked smoking. This may suggest independent roles for CR and traditional dependence as determinants of smoking, and highlights the importance of assessing behavioral CR outcomes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Nicotine Dependence, “Background” and Cue-Induced Craving and Smoking in the Laboratory

    Science.gov (United States)

    Dunbar, Michael S.; Shiffman, Saul; Kirchner, Thomas; Tindle, Hilary; Scholl, Sarah

    2014-01-01

    Background Nicotine dependence has been associated with higher “background” craving and smoking, independent of situational cues. Due in part to conceptual and methodological differences across past studies, the relationship between dependence and cue-reactivity (CR; e.g., cue-induced craving and smoking) remains unclear. Methods 207 daily smokers completed six pictorial CR sessions (smoking, negative affect, positive affect, alcohol, smoking prohibitions, and neutral). Individuals rated craving before (background craving) and after cues, and could smoke following cue exposure. Session videos were coded to assess smoking. Participants completed four nicotine dependence measures. Regression models assessed the relationship of dependence to cue-independent (i.e., pre-cue) and cue-specific (i.e., pre-post cue change for each cue, relative to neutral) craving and smoking (likelihood of smoking, latency to smoke, puff count). Results Dependence was associated with background craving and smoking, but did not predict change in craving across the entire sample for any cue. Among alcohol drinkers, dependence was associated with greater increases in craving following the alcohol cue. Only one dependence measure (Wisconsin Inventory of Smoking Dependence Motives) was consistently associated with smoking reactivity (higher likelihood of smoking, shorter latency to smoke, greater puff count) in response to cues. Conclusion While related to cue-independent background craving and smoking, dependence is not strongly associated with laboratory cue-induced craving under conditions of minimal deprivation. Dependence measures that incorporate situational influences on smoking correlate with greater cue-provoked smoking. This may suggest independent roles for CR and traditional dependence as determinants of smoking, and highlights the importance of assessing behavioral CR outcomes. PMID:25028339

  16. Predictors of Nicotine Dependence in Adolescents: Symptoms of Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Yeh, Ta-Chuan; Wang, Sheng-Chiang; Chang, Yu-Tien; Yeh, Chin-Bin

    2017-05-01

    Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) have been associated with the use of cigarettes, but little is known about the impact of the subthreshold symptoms of BD or ADHD on the course of nicotine dependence. Identifying the links is essential for elucidating the pathway and supporting the development of nicotine prevention strategies for adolescents. Participants (n = 3322) aged 15-17 years completed the Chinese version of the ADHD Self-Report Scale and the Mood Disorder Questionnaire. The modified Fagerström Tolerance Questionnaire was completed to measure their nicotine use or dependence. Mediation analyses were performed to explore the relationship of two predictors. The prevalence rates of cigarette smoking and nicotine dependence in this study were 14.4% and 2.3%, respectively. Male gender (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.60-3.30), subclinical symptoms of ADHD (OR 1.34; 95% CI 1.04-1.71), clinical symptoms of ADHD (OR 1.69; 95% CI 1.08-2.66), and symptoms of BD (OR 1.59; 95% CI1.09 to 2.32) were associated with nicotine use. Male gender (OR 4.60; 95% CI 1.41-14.98) and symptoms of BD (OR 6.14; 95% CI 3.37-11.18), but not symptoms of ADHD, were associated with nicotine dependence. In mediation analyses, we found that the effect of ADHD symptoms was no longer significant after controlling for symptoms of BD, and the mediation ratio (P M ) was 0.39. Our findings suggest that mood disturbances other than symptoms of ADHD are more likely to be a key predictor of nicotine dependence among adolescents. The conclusions may improve our understanding of the course of nicotine dependence and help to promote potential health policy for nicotine control among youths.

  17. Elevated Risk of Nicotine Dependence Among Sib-pairs Discordant for Maternal Smoking During Pregnancy

    Science.gov (United States)

    Shenassa, Edmond D.; Papandonatos, George D.; Rogers, Michelle L.; Buka, Stephen L.

    2015-01-01

    Background Compelling evidence links maternal smoking during pregnancy with elevated risk of nicotine dependence among the offspring. However, no study to date has examined the maternal smoking during pregnancy-nicotine dependence link among sibling-pairs discordant for maternal smoking during pregnancy. We tested two hypotheses that, if supported, suggest that the maternal smoking during pregnancy-nicotine dependence link may be physiologically mediated. Methods Study participants were adult offspring of women enrolled in the Providence and Boston sites of the Collaborative Perinatal Project (1959–1966). Approximately 10% of these adult offspring (average age: 39.6 years) were enrolled in the New England Family Study (n = 1,783), a follow-up study that oversampled families with multiple siblings. Logistic regression models predicting maternal smoking during pregnancy risk on various prospectively collected smoking and marijuana use outcomes, including nicotine dependence, were fit using models that allowed between-mother effects of maternal smoking during pregnancy exposure to differ from within-mother effects. In the absence of significant effect heterogeneity, we calculated a combined estimate. Results Maternal smoking during pregnancy predicted progression from weekly smoking to nicotine dependence (odds ratio = 1.4 [95% confidence interval = 1.2, 1.8]), but not weekly smoking or progression to marijuana dependence. Conclusions Current evidence from sibling-pairs discordant for maternal smoking during pregnancy is consistent with previous reports of a dose–response association between maternal smoking during pregnancy and nicotine dependence, as well as of up-regulation of nicotine receptors among animals exposed to maternal smoking during pregnancy. Together, they provide support for the existence of a physiologically mediated link between maternal smoking during pregnancy and nicotine dependence. PMID:25767988

  18. The μ-opioid receptor gene and smoking initiation and nicotine dependence

    Directory of Open Access Journals (Sweden)

    Kendler Kenneth S

    2006-08-01

    Full Text Available Abstract The gene encoding the mu-opioid receptor (OPRM1 is reported to be associated with a range of substance dependence. Experiments in knockout mice indicate that the mu-opioid receptor may mediate reinforcing effects of nicotine. In humans, opioid antagonist naltrexone may reduce the reinforcing effects of tobacco smoking. Additionally, the OPRM1 gene is located in a region showing linkage to nicotine dependence. The OPRM1 is thus a plausible candidate gene for smoking behavior. To investigate whether OPRM1 contributes to the susceptibility of smoking initiation and nicotine dependence, we genotyped 11 SNPs in the gene for 688 Caucasian subjects of lifetime smokers and nonsmokers. Three SNPs showed nominal significance for smoking initiation and one reached significance for nicotine dependence. The global test for three-marker (rs9479757-rs2075572-rs10485057 haplotypes was significant for smoking initiation (p = 0.0022. The same three-marker haplotype test was marginal (p = 0.0514 for nicotine dependence. These results suggest that OPRM1 may be involved in smoking initiation and nicotine dependence.

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

    Science.gov (United States)

    Balbani, Aracy Pereira Silveira; Montovani, Jair Cortez

    2005-01-01

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

  20. Abandonment of nicotine dependence treatment: A cohort study

    Directory of Open Access Journals (Sweden)

    Maritza Muzzi Cardozo Pawlina

    Full Text Available CONTEXT AND OBJECTIVE: Non-adherence to treatment is one of the hindering factors in the process of smoking cessation. This study aimed to compare sociodemographic characteristics, smoking status and motivation among smokers who maintained or abandoned treatment to stop smoking, and to analyze associations between sociodemographic factors and smoking. DESIGN AND SETTING: Cohort study on 216 smokers who were attended at healthcare units in Cuiabá, Mato Grosso. METHODS: The instruments used were the Fagerström, URICA and CAGE questionnaires. Data from the initial evaluation was analyzed using the two-proportion test (α < 0.05. The patients were monitored for six months and those who abandoned treatment were accounted for. Bivariate analysis was conducted, using crude prevalence ratios and 5% significance level (P < 0.05, with abandonment of treatment as the outcome variable. Associations with P < 0.20 were selected for multiple robust Poisson regression (RPa. RESULTS: The abandonment rate was 34.26%. Males and individuals in the 20-39 age group, in employment, with low motivation, with shorter time smoking and lower tobacco intake predominated in the dropout group. In the final model, gender (RPa 1.47; 95% CI: 1.03-2.10 and age group (RPa 3.77; 95% CI: 1.47-9.67 remained associated with abandonment. CONCLUSION: Males and individuals in the 20-39 age group, in employment, with low motivation, with shorter time smoking and lower tobacco intake more frequently abandoned the treatment. Male gender and younger age group were associated with abandonment of nicotine dependence treatment.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Moylan Steven

    2012-10-01

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

  3. Everyday discrimination is associated with nicotine dependence among African American, Latino, and White smokers.

    Science.gov (United States)

    Kendzor, Darla E; Businelle, Michael S; Reitzel, Lorraine R; Rios, Debra M; Scheuermann, Taneisha S; Pulvers, Kim; Ahluwalia, Jasjit S

    2014-06-01

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

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

    Science.gov (United States)

    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

  5. Smoking history, nicotine dependence and opioid use in patients with chronic non-malignant pain

    DEFF Research Database (Denmark)

    Plesner, K; Jensen, H I; Højsted, J

    2016-01-01

    BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both...... pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried...... as in the general population. The prevalence of patients using opioids was 54% and the prevalence of addiction to opioids was 6%. No significant differences in addiction were found between the different smoking groups, but smokers and former smokers using nicotine tended to use opioids more frequently and at higher...

  6. Nicotine and alcohol dependence in patients with comorbid attention-deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    Ohlmeier, Martin D; Peters, Karsten; Kordon, Andreas; Seifert, Jürgen; Wildt, Bert Te; Wiese, Birgitt; Ziegenbein, Marc; Emrich, Hinderk M; Schneider, Udo

    2007-01-01

    Several studies have shown that attention-deficit/hyperactivity disorder (ADHD) represents a significant risk factor for the onset and development of an addiction. Thirty-five per cent of adult ADHD patients are known to be addicted to alcohol. Many ADHD patients also have an increased nicotine consumption, which typically, leads to an improvement of attention, ability to concentrate and control of impulses. There may be pathophysiological connections here. On the other hand, it can also be assumed that there is a high prevalence of addicted patients with undiagnosed ADHD. Ninety-one adult alcohol-dependent patients were examined for ADHD in this study, using the Wender Utah Rating Scale (WURS-k), Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptom check-list for ADHD and the Conners' Adult ADHD Rating Scales (CAARS, Long Version). The patients were divided into diagnostic sub-groups according to DSM-IV (inattentive type, impulsive type, combined type). Nicotine consumption was investigated using the Fagerström Test of Nicotine Dependence (FTND) and then graded as 'minimal', 'average' or 'high' nicotine dependence. There were 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the patients addicted to alcohol, who showed evidence of ADHD in childhood. With the help of CAARS, it could be demonstrated that 33.3% of the patients who fulfilled the diagnostic criteria of ADHD, according to DSM-IV, had persisting ADHD in adulthood. The FTND showed a statistically significant difference in nicotine dependence between alcohol-dependent patients with and without ADHD in childhood. Patients numbering 76.2% with ADHD, demonstrated an 'average to high' level of nicotine dependence compared to 45.7% of those patients without ADHD. Furthermore, the number of patients not addicted to nicotine (19%) was significantly lower than among those without ADHD (36.6%) (P = 0.029). The results of this investigation reveal that a large number of ADHD patients suffer

  7. A hierarchical instrumental decision theory of nicotine dependence.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  9. Multiple tobacco use and increased nicotine dependence among people with disabilities.

    Science.gov (United States)

    Soule, Eric K; Pomeranz, Jamie L; Moorhouse, Michael D; Barnett, Tracey E

    2015-04-01

    People with disabilities (PWD) are at greatest risk for tobacco use compared to people without disabilities. However, little is known about the use of multiple types of tobacco by PWD. The purpose of this study was to examine nicotine dependence among a sample of PWD who use multiple types tobacco products. We hypothesized that individuals who used multiple forms of tobacco would have higher levels of nicotine dependence. A tobacco survey was administered to clients who use tobacco and receive services from an organization that provides independent living services to PWD. The self-report brief survey included measures of nicotine dependence and items indicating the types of tobacco products participants used. A total of 113 male and female participants with disabilities (mean age = 51.7, SD = 10.1) participated in the study. Multiple tobacco use was reported by 16.8% of the participants and was significantly associated with nicotine dependence. Compared to single tobacco product users, multiple tobacco users were more likely to use tobacco within the first 30 min of waking, believe tobacco the first thing in the morning would be the most difficult to give up, and find it hard to not use tobacco in prohibited locations. The use of multiple types of tobacco products among PWD disability is relatively common and is associated with greater nicotine dependence. Tobacco cessation interventions targeting PWD should consider the addressing unique challenges of preventing different types of tobacco products. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Use Behaviors, Dependence, and Nicotine Exposure Associated with Ad Libitum Cigar Smoking

    Science.gov (United States)

    Claus, Eric D.; Moeller, Benjamin C.; Harbour, Darlene; Kuehl, Philip J.; McGuire, Michael; Vivar, Juan C.; Schroeder, Megan J.

    2018-01-01

    Objectives To examine factors important to cigar smoking and subsequent nicotine exposure, we evaluated the impact of cigar type, cigarette smoking history, and inhalation behaviors on nicotine dependence, smoking topography, and biomarkers of exposure in current exclusive cigar smokers. Methods Adult, exclusive cigar smokers (N = 77) were recruited based on cigar type, cigarette smoking history, and self-reported inhalation behaviors. Participants smoked their own brand product ad libitum for up to one hour; dependence symptoms, smoking topography, and biomarkers of exposure were assessed. Results Cigar smokers showed low levels of dependence. Cigar smoking alleviated withdrawal and craving symptoms, increased plasma nicotine concentration, and increased exhaled CO. Multiple regression analyses indicate that inhalation behaviors were associated with increased dependence and greater reductions in withdrawal symptoms upon cigar smoking. Large cigar smokers smoked longer and smoked more tobacco than small cigar and cigarillo smokers. Furthermore, large cigar smokers and self-reported inhalers were exposed to more nicotine than small cigar smokers and non-inhalers. Conclusions Our study suggests that cigar type and smoking behaviors affect dependence and nicotine exposure upon cigar smoking. These findings provide additional insight into the substantial risks associated with cigar smoking. PMID:29516029

  11. Effect of variation in BDNF Val(66)Met polymorphism, smoking, and nicotine dependence on symptom severity of depressive and anxiety disorders.

    Science.gov (United States)

    Jamal, Mumtaz; Van der Does, Willem; Penninx, Brenda W J H

    2015-03-01

    Smoking, especially nicotine dependence is associated with more severe symptoms of depression and anxiety disorders. However, the mechanisms underlying this association are unclear. We investigated the effect of brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism on the severity of depressive and anxiety symptoms in never-smokers, former smokers, non-dependent, and nicotine-dependent smokers with a current diagnosis of depression and/or anxiety. Patients with depressive or anxiety disorders and with available BDNF Val(66)Met polymorphism data (N=1271) were selected from Netherlands Study of Depression and Anxiety (NESDA). Dependent variables were severity of symptoms. Independent variables were smoking status and BDNF genotype. Age, sex, education, recent negative life events, alcohol use, body mass index, and physical activity were treated as covariates. After controlling for covariates, nicotine-dependent smokers had more severe depressive symptoms than non-dependent smokers, former and never-smokers. The latter three groups did not differ in severity of depression. In Val(66)Val carriers, nicotine-dependent smokers had more severe symptoms of depression and anxiety than the other three groups, which were comparable in symptom severity. In Met(66) carriers, there were no group differences on severity of depression and anxiety. Nicotine dependence was the strongest predictor of severity of symptoms only in Val(66)Val carriers. In patients with a current diagnosis of depression or anxiety, the relationship between nicotine dependence and symptom severity may be moderated by BDNF Val(66)Met. These results suggest that inherent genetic differences may be crucial for the worse behavioral outcome of nicotine, and that Val(66)Val carriers may benefit most in mental health from smoking cessation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; 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

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

    International Nuclear Information System (INIS)

    Xu, Yuan; Cardell, Lars-Olaf

    2014-01-01

    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 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 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 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 2 receptors, but not those on B 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 some patients with asthma

  15. Smoking status, nicotine dependence and happiness in nine countries of the former Soviet Union.

    Science.gov (United States)

    Stickley, Andrew; Koyanagi, Ai; Roberts, Bayard; Leinsalu, Mall; Goryakin, Yevgeniy; McKee, Martin

    2015-03-01

    The US Food and Drug Administration has established a policy of substantially discounting the health benefits of reduced smoking in its evaluation of proposed regulations because of the cost to smokers of the supposed lost pleasure they suffer by no longer smoking. This study used data from nine countries of the former Soviet Union (fSU) to explore this association in a setting characterised by high rates of (male) smoking and smoking-related mortality. Data came from a cross-sectional population-based study undertaken in 2010/2011 in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine. Information was collected from 18 000 respondents aged ≥18 on smoking status (never, ex-smoking and current smoking), cessation attempts and nicotine dependence. The association between these variables and self-reported happiness was examined using ordered probit regression analysis. In a pooled country analysis, never smokers and ex-smokers were both significantly happier than current smokers. Smokers with higher levels of nicotine dependence were significantly less happy than those with a low level of dependence. This study contradicts the idea that smoking is associated with greater happiness. Moreover, of relevance for policy in the fSU countries, given the lack of public knowledge about the detrimental effects of smoking on health but widespread desire to quit reported in recent research, the finding that smoking is associated with lower levels of happiness should be incorporated in future public health efforts to help encourage smokers to quit by highlighting that smoking cessation may result in better physical and emotional health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Cherry Wongtrakool

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

  17. The relative impact of nicotine dependence, other substance dependence, and gender on Bechara Gambling Task performance.

    Science.gov (United States)

    Businelle, Michael S; Apperson, Megan R; Kendzor, Darla E; Terlecki, Meredith A; Copeland, Amy L

    2008-12-01

    Individuals with substance use disorders (SUDs) tend to focus more on immediate, rather than cumulative, consequences of their actions on measures of decision-making. This type of decision-making may contribute to continued substance use. The present study compared the performance of four groups of individuals on one measure of decision-making, the Bechara Gambling Task (BGT). The groups were (a) heavy smokers with comorbid substance dependence (n = 40), (b) heavy smokers with no history of substance dependence (n = 19), (c) substance dependent never smokers (n = 26), and (d) never smokers with no history of substance dependence (n = 34). Analysis revealed that there were no significant main effects of gender or SUD status. However, a significant gender by SUD status interaction was found, such that men with an SUD performed more poorly on the BGT than men without an SUD history. Women with and without an SUD both performed poorly on this task. Unexpectedly, no differences in BGT performance were found between smokers and nonsmokers. Overall, findings indicate that having an SUD, other than nicotine dependence, is correlated with poor BGT performance in men only. The BGT did not differentiate between women with and without SUDs, and therefore, may not be an appropriate measure of decision-making in women. (c) 2008 APA, all rights reserved.

  18. Psychiatric, psychosocial, and physical health correlates of co-occurring cannabis use disorders and nicotine dependence.

    Science.gov (United States)

    Peters, Erica N; Schwartz, Robert P; Wang, Shuai; O'Grady, Kevin E; Blanco, Carlos

    2014-01-01

    Several gaps in the literature on individuals with co-occurring cannabis and tobacco use exist, including the extent of psychiatric, psychosocial, and physical health problems. We examine these gaps in an epidemiological study, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), of a large, nationally representative sample. The sample was drawn from Wave 2 NESARC respondents (N=34,653). Adults with current cannabis use disorders and nicotine dependence (CUD+ND) (n=74), CUD only (n=100), and ND only (n=3424) were compared on psychiatric disorders, psychosocial correlates (e.g., binge drinking; partner violence), and physical health correlates (e.g., medical conditions). Relative to those with CUD only, respondents with CUD+ND were significantly more likely to meet criteria for bipolar disorder, Clusters A and B personality disorders, and narcissistic personality disorder, and reported engaging in a significantly higher number of antisocial behaviors. Relative to those with ND only, respondents with CUD+ND were significantly more likely to meet criteria for bipolar disorder, anxiety disorders, and paranoid, schizotypal, narcissistic, and borderline personality disorders; were significantly more likely to report driving under the influence of alcohol and being involved in partner violence; and reported engaging in a significantly higher number of antisocial behaviors. CUD+ND was not associated with physical health correlates. Poor treatment outcomes for adults with co-occurring cannabis use disorders and nicotine dependence may be explained in part by differences in psychiatric and psychosocial problems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. CHRNA3 genotype, nicotine dependence, lung function and disease in the general population

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Nordestgaard, Børge G; Bojesen, Stig E

    2012-01-01

    The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case-control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown. We...... genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded. In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever...

  20. Neural bases of pharmacological treatment of nicotine dependence - insights from functional brain imaging: a systematic review

    NARCIS (Netherlands)

    Menossi, Henrique Soila; Goudriaan, Anna E.; de Azevedo-Marques Périco, Cintia; Nicastri, Sérgio; de Andrade, Arthur Guerra; D'Elia, Gilberto; Li, Chiang-Shan R.; Castaldelli-Maia, João Mauricio

    2013-01-01

    Nicotine dependence is difficult to treat, and the biological mechanisms that are involved are not entirely clear. There is an urgent need to develop better drugs and more effective treatments for clinical practice. A critical step towards accelerating progress in medication development is to

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Noble, E.P.; Fitch, R.J.; Syndulko, K. [Univ. of California, Los Angeles, CA (United States)] [and others

    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.

  4. Comparison of two nicotine dependence measures for use with Korean American Women: The FTND and AUTOS

    Directory of Open Access Journals (Sweden)

    Sun S. Kim

    2017-06-01

    Full Text Available This study compares psychometric properties of the Fagerström Test for Nicotine Dependence (FTND and Autonomy over Tobacco Scale (AUTOS, which are measures of nicotine dependence. This study is a secondary analysis of data obtained from a smoking cessation study conducted with 49 Korean American women. We compared the FTND and AUTOS assessed at baseline regarding their internal consistency reliability and concurrent and predictive validities. The AUTOS outperformed the FTND in reliability and concurrent validity by yielding a higher Cronbach’s alpha and having significant relationships with smoking-related variables such as age at smoking onset, perceived risks of quitting, and self-efficacy in quitting. In contrast, there was no relationship between the FTND and any of the variables. Both measures had a significant relationship with post-quit nicotine withdrawal symptoms but failed to predict abstinence at follow-ups. The AUTOS seems to be a better assessment tool for Korean American women than the FTND. Before fully adopting the AUTOS as a measure of nicotine dependence for this group, factor structure of the scale should be tested with a larger sample of Korean American women.

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

    Science.gov (United States)

    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

  6. Effect of variation in BDNF Val(66)Met polymorphism, smoking, and nicotine dependence on symptom severity of depressive and anxiety disorders

    NARCIS (Netherlands)

    Jamal, Mumtaz; Van der Does, Willem; Penninx, Brenda W. J. H.

    2015-01-01

    Background: Smoking, especially nicotine dependence is associated with more severe symptoms of depression and anxiety disorders. However, the mechanisms underlying this association are unclear. We investigated the effect of brain-derived neurotrophic factor (BDNF) VaI(66)Met polymorphism on the

  7. Validation of the nicotine dependence syndrome scale (NDSS): a criterion-group design contrasting chippers and regular smokers

    OpenAIRE

    Shiffman, Saul; Sayette, Michael A.

    2005-01-01

    The nicotine dependence syndrome scale (NDSS) is a new multi-dimensional measure of nicotine dependence, yielding five scores for different aspects of dependence as well as a total score. In this study, we tested the NDSS in a young adult sample (mean age = 24), using an extreme-groups comparison between non-dependent smokers (chippers, n = 123) and regular smokers (n = 130). Scores on each NDSS subscale strongly discriminated between the groups, with the NDSS-total discriminating them almost...

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

    Science.gov (United States)

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

    2014-03-01

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

  9. Personality Traits and Psychopathology in Nicotine and Opiate Dependents Using the Gateway Drug Theory

    Directory of Open Access Journals (Sweden)

    Bahareh Amirabadi

    2015-03-01

    Full Text Available Objectives: According to the gateway drug theory, tobacco use is a predisposing factor for future substance abuse. This study was conducted to compare nicotine and opiate dependents to identify the differences between their personality traits and psychopathology that makes them turn to other substances after cigarette smoking. Methods: A causal-comparative study was conducted. Three groups were randomly selected: nicotine dependents, opiate dependents and ordinary individuals (non-dependent population. Cloninger’s Temperament and Character Inventory-Revised, the Fagerstrom Test for Nicotine Dependence, Maudsley Addiction Profile, the Beck Depression Inventory, and Beck Anxiety Inventory were used to collect data. Analysis of variance was used to analyze data. Results: Opiate dependents had higher ‘novelty seeking’ and lower ‘cooperativeness’ scores as compared to the other two groups. They also had higher anxiety and depression scores than the other two groups. Discussion: Higher ‘novelty seeking’ and lower ‘cooperativeness’ scores are important personality traits predicting

  10. Predictors of the Nicotine Dependence Behavior Time to the First Cigarette in a Multiracial Cohort.

    Science.gov (United States)

    Branstetter, Steven A; Mercincavage, Melissa; Muscat, Joshua E

    2015-07-01

    The time to first cigarette of the day (TTFC) is a strong indicator of nicotine dependence behaviors such as nicotine uptake and quit success in young and older smokers. There are substantial differences in levels of nicotine dependence by race and ethnic group. Data from Wave III of the multiracial National Longitudinal Study of Adolescent Health were analyzed for young smokers between the ages of 21 and 28 (N = 1,425). Time to first cigarette data was compared between Hispanic, White, Black, Native American, and Asian smokers. Black smokers were significantly more likely to smoke within 5min of waking than White, Hispanic, and Asian smokers. Lower personal income predicted smoking within 5min of waking for both White and Black smokers. For White smokers, increased number of cigarettes per day and increased years of smoking also predicted smoking within 5min of waking. The number of days smoked or number of cigarettes per day did not predict smoking within 5min of waking among smokers. The higher prevalence of early TTFC among Blacks indicates increased nicotine and carcinogen exposure, and may help explain the increased lung cancer rates and failed cessation attempts among Black smokers. TTFC may be an important screening item, independent of cigarettes per day, for clinicians and interventions to identify those at highest risk for cessation failure and disease risk. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Nicotine Effects on the Impact of Stress

    Science.gov (United States)

    2016-03-01

    administration ceased: nicotine may have some beneficial effects, but nicotine withdrawal is unambiguously detrimental. Our funding period ended on...effects of nicotine . Our research involves a model of nicotine use (voluntary intravenous self- administration of nicotine in rats) and PTSD (fear... nicotine or nicotine withdrawal affect the development of conditioned fear under circumstances where nicotine self- administration is discontinued

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

    Science.gov (United States)

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

    2015-04-01

    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. 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. 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). 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    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). Conclusion Only the intensity of smoking consumption had an influence over the cardiac autonomic modulation of the assessed tobacco smokers. Tobacco smokers with severe intensity of smoking consumption presented a lower autonomic modulation than those with moderate intensity. PMID:27142649

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

    Directory of Open Access Journals (Sweden)

    Ana Paula Soares dos Santos

    2016-01-01

    Full Text Available Abstract 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. 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.

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

    Science.gov (United States)

    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.

  16. A Role for the DRD4 Exon III VNTR in Modifying the Association Between Nicotine Dependence and Neuroticism

    NARCIS (Netherlands)

    Ellis, J.A.; Olssen, C.A.; Moore, E.; Greenwood, P.A.; Ven, M.O.M. van de; Patton, G.C.

    2011-01-01

    Introduction: Neurotic psychopathology has been extensively examined as a risk factor for nicotine dependence (ND). Genetic stratification may partially explain variability in risk estimates. Genetic variants that compromise dopaminergic neurotransmission may motivate exposure to

  17. Regulation of Nicotine Tolerance by Quorum Sensing and High Efficiency of Quorum Quenching Under Nicotine Stress in Pseudomonas aeruginosa PAO1

    Directory of Open Access Journals (Sweden)

    Huiming Tang

    2018-03-01

    Full Text Available Quorum sensing (QS regulates the behavior of bacterial populations and promotes their adaptation and survival under stress. As QS is responsible for the virulence of vast majority of bacteria, quorum quenching (QQ, the interruption of QS, has become an attractive therapeutic strategy. However, the role of QS in stress tolerance and the efficiency of QQ under stress in bacteria are seldom explored. In this study, we demonstrated that QS-regulated catalase (CAT expression and biofilm formation help Pseudomonas aeruginosa PAO1 resist nicotine stress. CAT activity and biofilm formation in wild type (WT and ΔrhlR strains are significantly higher than those in the ΔlasR strain. Supplementation of ΔlasI strain with 3OC12-HSL showed similar CAT activity and biofilm formation as those of the WT strain. LasIR circuit rather than RhlIR circuit is vital to nicotine tolerance. Acylase I significantly decreased the production of virulence factors, namely elastase, pyocyanin, and pyoverdine under nicotine stress compared to the levels observed in the absence of nicotine stress. Thus, QQ is more efficient under stress. To our knowledge, this is the first study to report that QS contributes to nicotine tolerance in P. aeruginosa. This work facilitates a better application of QQ for the treatment of bacterial infections, especially under stress.

  18. Cancer Patients Enrolled in a Smoking Cessation Clinical Trial: Characteristics and Correlates of Smoking Rate and Nicotine Dependence

    Directory of Open Access Journals (Sweden)

    Andrew Miele

    2018-01-01

    Full Text Available Introduction. A substantial proportion of cancer patients continue to smoke after their diagnosis but few studies have evaluated correlates of nicotine dependence and smoking rate in this population, which could help guide smoking cessation interventions. Aim. This study evaluated correlates of smoking rate and nicotine dependence among 207 cancer patients. Methods. A cross-sectional analysis using multiple linear regression evaluated disease, demographic, affective, and tobacco-seeking correlates of smoking rate and nicotine dependence. Smoking rate was assessed using a timeline follow-back method. The Fagerström Test for Nicotine Dependence measured levels of nicotine dependence. Results. A multiple linear regression predicting nicotine dependence showed an association with smoking to alleviate a sense of addiction from the Reasons for Smoking scale and tobacco-seeking behavior from the concurrent choice task (p.05. Multiple linear regression predicting prequit showed an association with smoking to alleviate addiction (p<.05. ANOVA showed that Caucasian participants reported greater rates of smoking compared to other races. Conclusions. The results suggest that behavioral smoking cessation interventions that focus on helping patients to manage tobacco-seeking behavior, rather than mood management interventions, could help cancer patients quit smoking.

  19. Neuroadaptive Changes Associated with Smoking: Structural and Functional Neural Changes in Nicotine Dependence

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    Chantal Martin-Soelch

    2013-02-01

    Full Text Available Tobacco smoking is the most frequent form of substance abuse. We provide a review of the neuroadaptive changes evidenced in human smokers with regard to the current neurobiological models of addiction. Addiction is thought to result from an interplay between positive and negative reinforcement. Positive reinforcing effects of the drugs are mediated by striatal dopamine release, while negative reinforcement involves the relief of withdrawal symptoms and neurobiological stress systems. In addition, drug-related stimuli are attributed with excessive motivational value and are thought to exert a control on the behavior. This mechanism plays a central role in drug maintenance and relapse. Further neuroadaptive changes associated with chronic use of the drug consist of reduced responses to natural rewards and in the activation of an antireward system, related to neurobiological stress systems. Reduced inhibitory cognitive control is believed to support the development and the maintenance of addiction. The findings observed in human nicotine dependence are generally in line with these models. The current state of the research indicates specific neuroadaptive changes associated with nicotine addiction that need to be further elucidated with regard to their role in the treatment of nicotine dependence.

  20. Chronic Nicotine Mitigates Aberrant Inhibitory Motor Learning Induced by Motor Experience under Dopamine Deficiency.

    Science.gov (United States)

    Koranda, Jessica L; Krok, Anne C; Xu, Jian; Contractor, Anis; McGehee, Daniel S; Beeler, Jeff A; Zhuang, Xiaoxi

    2016-05-11

    Although dopamine receptor antagonism has long been associated with impairments in motor performance, more recent studies have shown that dopamine D2 receptor (D2R) antagonism, paired with a motor task, not only impairs motor performance concomitant with the pharmacodynamics of the drug, but also impairs future motor performance once antagonism has been relieved. We have termed this phenomenon "aberrant motor learning" and have suggested that it may contribute to motor symptoms in movement disorders such as Parkinson's disease (PD). Here, we show that chronic nicotine (cNIC), but not acute nicotine, treatment mitigates the acquisition of D2R-antagonist-induced aberrant motor learning in mice. Although cNIC mitigates D2R-mediated aberrant motor learning, cNIC has no effect on D1R-mediated motor learning. β2-containing nicotinic receptors in dopamine neurons likely mediate the protective effect of cNIC against aberrant motor learning, because selective deletion of β2 nicotinic subunits in dopamine neurons reduced D2R-mediated aberrant motor learning. Finally, both cNIC treatment and β2 subunit deletion blunted postsynaptic responses to D2R antagonism. These results suggest that a chronic decrease in function or a downregulation of β2-containing nicotinic receptors protects the striatal network against aberrant plasticity and aberrant motor learning induced by motor experience under dopamine deficiency. Increasingly, aberrant plasticity and aberrant learning are recognized as contributing to the development and progression of movement disorders. Here, we show that chronic nicotine (cNIC) treatment or specific deletion of β2 nicotinic receptor subunits in dopamine neurons mitigates aberrant motor learning induced by dopamine D2 receptor (D2R) blockade in mice. Moreover, both manipulations also reduced striatal dopamine release and blunt postsynaptic responses to D2R antagonists. These results suggest that chronic downregulation of function and/or receptor

  1. Evaluating Nicotine Craving, Withdrawal, and Substance Use as Mediators of Smoking Cessation in Cocaine- and Methamphetamine-Dependent Patients.

    Science.gov (United States)

    Magee, Joshua C; Lewis, Daniel F; Winhusen, Theresa

    2016-05-01

    Smoking is highly prevalent in substance dependence, but smoking-cessation treatment (SCT) is more challenging in this population. To increase the success of smoking cessation services, it is important to understand potential therapeutic targets like nicotine craving that have meaningful but highly variable relationships with smoking outcomes. This study characterized the presence, magnitude, and specificity of nicotine craving as a mediator of the relationship between SCT and smoking abstinence in the context of stimulant-dependence treatment. This study was a secondary analysis of a randomized, 10-week trial conducted at 12 outpatient SUD treatment programs. Adults with cocaine and/or methamphetamine dependence (N = 538) were randomized to SUD treatment as usual (TAU) or TAU+SCT. Participants reported nicotine craving, nicotine withdrawal symptoms, and substance use in the week following a uniform quit attempt of the TAU+SCT group, and self-reported smoking 7-day point prevalence abstinence (verified by carbon monoxide) at end-of-treatment. Bootstrapped regression models indicated that, as expected, nicotine craving following a quit attempt mediated the relationship between SCT and end-of-treatment smoking point prevalence abstinence (mediation effect = 0.09, 95% CI = 0.04% to 0.14%, P substance use were not significant mediators (Ps > .05, substance dependence. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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

  3. Nicotine dependence in the mental disorders, relationship with clinical indicators, and the meaning for the user

    Directory of Open Access Journals (Sweden)

    Renata Marques de Oliveira

    2014-08-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  5. Nicotine Dependence

    Science.gov (United States)

    ... depression and smoking. People who have depression, schizophrenia, post-traumatic stress disorder (PTSD) or other forms of mental illness are more ... resistance, which can set the stage for the development of type 2 diabetes. If you have diabetes, ...

  6. Nicotine Dependence in Adolescence and Physical Health Symptoms in Early Adulthood.

    Science.gov (United States)

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

    2016-05-01

    To examine the prospective associations of Diagnostic and Statistical Manual of Mental Disorders nicotine dependence (ND) and other individual and parental factors in adolescence on self-reported health symptoms in early adulthood. Multiethnic prospective longitudinal cohort of adolescents from grades 6-10 and a parent (N = 908) from the Chicago Public Schools. Adolescents were interviewed five times at 6-month intervals (Waves 1-5) and once 4.5 years later (Wave 6). Parents were interviewed annually three times (W1, W3, W5). Multivariate regressions estimated prospective associations of Diagnostic and Statistical Manual of Mental Disorders ND, other individual and familial risk factors in adolescence (mean age 16.6) on physical health symptoms in early adulthood (mean age 21.3), controlling for health symptoms in adolescence. Levels of health symptoms declined from adolescence to early adulthood, except among dependent smokers. Nicotine dependent adolescents reported more health symptoms as young adults than nonsmokers and nondependent smokers, especially if depressed. ND and health symptoms in adolescence were the strongest predictors of health in early adulthood. These two adolescent factors, depression, and the familial factors of parental ND, depression and health conditions, each independently predicted health symptoms in young adulthood. Females reported more symptoms than males. There is continuity of health status over time. ND, depression, and parental factors in adolescence contribute to poor health in early adulthood. The findings highlight not only the role of adolescent behavior, but the importance of the family in the development of young adult health. Reducing smoking, particularly ND, and depression among adolescents and parents will decrease physical health burden. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Levelling the Playing Field: the FDA's Regulation of Nicotine Dependence Products

    OpenAIRE

    Szubin, Adam J.

    1999-01-01

    There is a great need for the increased development and use of nicotine dependence products (NDPs) in this country. A creative regulatory approach, such as the FDA brought to tobacco regulation, could do an enormous amount of good. In the field of NDPs, as in every area of drug regulation, a new regulatory approach will bring with it costs and benefits. As our knowledge advances, the FDA should not be slow to adopt the same aggressive yet flexible approach to NDPs that it has adopted towards ...

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

    NARCIS (Netherlands)

    Niemegeers, P.; Dumont, G.J.H.; Quisenaerts, C.; Morrens, M.; Boonzaier, J.; Fransen, E.; Bruijn, E.R.A. de; Hulstijn, W.; Sabbe, B.G.C.

    2014-01-01

    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

  9. Smoking, nicotine dependence, and motives to quit in Asian American versus Caucasian college students.

    Science.gov (United States)

    Bowen, Sarah; Kurz, Andrew S

    2012-10-01

    Few smoking cessation programs are designed for college students, a unique population that may categorically differ from adolescents and adults, and thus may have different motivations to quit than the general adult population. Understanding college student motives may lead to better cessation interventions tailored to this population. Motivation to quit may differ, however, between racial groups. The current study is a secondary analysis examining primary motives in college student smokers, and differences between Asian American and Caucasian students in smoking frequency, nicotine dependence, and motives to quit. Participants (N = 97) listed personal motives to quit cigarette smoking, which were then coded into categories: health, personal relationships (e.g., friends, family, romantic partners), self-view (e.g., "addicted" or "not in control"), image in society, impact on others or the environment (e.g., second-hand smoke, pollution), and drain on personal resources (e.g., money, time). Mean number of motives were highest in the category of health, followed by personal relationships, drain on resources, self-view, image, and impact. Asian American students listed significantly fewer motives in the categories of health, self-view and image, and significantly more in the category of personal relationships than Caucasian students. Nicotine dependence was significantly higher for Asian American students. However, frequency of smoking did not differ between groups. Results may inform customization of smoking cessation programs for college students and address relevant culturally specific factors of different racial groups.

  10. SMOKING PREVALENCE AND NICOTINE DEPENDENCY AMONG YOUNG ADULT MEN AND FACTORS AFFECTING THIS

    Directory of Open Access Journals (Sweden)

    Cengiz Han ACIKEL

    2006-04-01

    Full Text Available Smoking is a health risk with highest mortality and morbidity among the worldwide preventable diseases. While military period is a risky period for starting smoking, it is also a good opportunity for population based education studies opposed to smoking. At this point of view it is important to know the smoking behaviors of enlisted people. This study was planned as cross-sectional research, and performed on 455 people selected by simple random method in Etimesgut Armed Unities School and Training Center Commandership at 2002. 53.8% of the participants reported that they had been smoking, and 9.9% of the participants reported that they had been smoking some times. The frequency of the symptoms of nicotine dependence was found as 16.2%. It was found that smoking frequency was very high in enlisted people and significant amount of them had had nicotine dependency symptoms. It is considered that educations about the hazards of smoking and activities for smoking cessation were needed during the military service. [TAF Prev Med Bull 2006; 5(2.000: 105-117

  11. Status of nicotine dependence and some related factors among waterpipe consumer women in Bushehr 2013-14

    Directory of Open Access Journals (Sweden)

    Maliha Saeed Firoozabadi

    2015-09-01

    Full Text Available Background: In recent years, water pipe smoking has been spread among adults especially in Asian African communities in the Middle East and Arabic countries. The aim of this study is determination of the nicotine dependence status and some related factors among women consumer in Bushehr. Material and Methods: 430 water pipe smoker women were examined in this cross-sectional study. Convenience and snowball sampling methods were used to collect data. After data collection, data were analyzed by SPSS software with using appropriate statistical tests. Results: In this study, 43.4% (N= 186 of women had moderate nicotine dependency. The overall mean and standard deviation score for nicotine dependence were 40.71±12.63. In this study, consumer’s education (p=0.004 and job (p=0.015, husband’s education (p=0.003, and job (p=0.043, history of water pipe smoking (p=0.000, intention to quit (p=0.021, and type of tobacco (p=0.003, significantly associated with nicotine dependence. Logit regression results showed that husband 's education level, age at onset of water pipe consuming and intention to quit water pipe explain nicotine dependence. Conclusion: Nicotine dependence among almost half of the consumer women was in average level and it is essential to design educational interventions for low socio - economic individuals particularly in teens and young people that this behavior has not institutionalized yet. Also for people who have no intention of quit water pipe, at first, we provide the conditions for their quitting through empowerment process and then encourage them to quit water pipe.

  12. Relationship of nicotine dependence, subsyndromal and pathological gambling, and other psychiatric disorders: data from the National Epidemiologic Survey on Alcohol and Related Conditions.

    Science.gov (United States)

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

    2009-03-01

    Nicotine dependence frequently co-occurs with subsyndromal and pathological levels of gambling. The relationship of nicotine dependence, levels of gambling pathology, and other psychiatric disorders, however, is incompletely understood. To use nationally representative data from the National Epidemiologic Survey on Alcohol and Related Conditions to examine the influence of DSM-IV nicotine dependence on the association between pathological gambling severities and other psychiatric disorders. Face-to-face interviews were conducted with 43,093 adults living in households and group-quarters in the United States. The main outcome measure was the co-occurrence of current nicotine dependence and Axis I and II disorders and severity of gambling based on the 10 inclusionary diagnostic criteria for pathological gambling. The study was conducted from 2001 to 2002. Among non-nicotine-dependent respondents, increasing gambling severity was associated with greater psychopathology for the majority of Axis I and II disorders. This pattern was not uniformly observed among nicotine-dependent subjects. Significant nicotine-by-gambling-group interactions were observed for multiple Axis I and II disorders. All significant interactions involved stronger associations between gambling and psychopathology in the non-nicotine-dependent group. In a large national sample, nicotine dependence influences the associations between gambling and multiple psychiatric disorders. Subsyndromal levels of gambling are associated with significant psychopathology. Nicotine dependence accounts for some of the elevated risks for psychopathology associated with subsyndromal and problem/pathological levels of gambling. Additional research is needed to examine specific prevention and treatment for individuals with problem/pathological gambling with and without nicotine dependence. ©Copyright 2009 Physicians Postgraduate Press, Inc.

  13. Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case-control study.

    Science.gov (United States)

    Agrawal, Arpana; Pergadia, Michele L; Saccone, Scott F; Hinrichs, Anthony L; Lessov-Schlaggar, Christina N; Saccone, Nancy L; Neuman, Rosalind J; Breslau, Naomi; Johnson, Eric; Hatsukami, Dorothy; Montgomery, Grant W; Heath, Andrew C; Martin, Nicholas G; Goate, Alison M; Rice, John P; Bierut, Laura J; Madden, Pamela A F

    2008-06-01

    The gamma-aminobutyric acid receptor A (GABRA) gene clusters on chromosomes 4 and 5 have been examined previously for their association with alcohol and drug dependence phenotypes. Compelling evidence suggests that GABRA2 is associated with alcohol and drug dependence. However, no study has investigated whether genes in the GABA(A) gene clusters are associated with nicotine dependence, an important phenotype with a high correlation to persistent smoking, the single most preventable cause of mortality world-wide. Using data on 1050 nicotine-dependent cases and 879 non-dependent smoking controls, we used logistic regression to examine the association between single nucleotide polymorphisms (SNPs) in 13 genes in the GABA(A) receptor system as well as GABBR2 (a GABA(B) gene). We found evidence for association between four SNPs in GABRA4, two SNPs in GABRA2 and one SNP in GABRE with nicotine dependence. These included a synonymous polymorphism in GABRA2 (rs279858), lying in a highly conserved region, which has been shown previously to be associated with alcohol and drug dependence. A non-synonymous polymorphism (rs16859834/rs2229940) in GABRA4, also highly conserved, was associated at P-value of 0.03. Significant haplotypes associated with nicotine dependence were found for GABRA2. No evidence for epistatic interactions were noted. Our study did not find evidence for an association between GABBR2 gene and nicotine dependence. Given the potential role of compounds that enhance GABAergic neurotransmission in smoking cessation research, these findings have enormous potential for informing the wider field of addiction research.

  14. Intra-subunit flexibility underlies activation and allosteric modulation of neuronal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Chrisman, Paul A; Podair, Julie I; Jobe, Emily M; Levandoski, Mark M

    2014-04-01

    Allosteric modulation is a general feature of nicotinic acetylcholine receptors, yet the structural components and movements important for conversions among functional states are not well understood. In this study, we examine the communication between the binding sites for agonist and the modulator morantel (Mor) of neuronal α3β2 receptors, measuring evoked currents of receptors expressed in Xenopus oocytes with the two-electrode voltage-clamp method. We hypothesized that movement along an interface of β sheets connecting the agonist and modulator sites is necessary for allosteric modulation. To address this, we created pairs of substituted cysteines that span the cleft formed where the outer β sheet meets the β sheet constituting the (-)-face of the α3 subunit; the three pairs were L158C-A179C, L158C-G181C and L158C-K183C. Employing a disulfide trapping approach in which bonds are formed between neighboring cysteines under oxidation conditions, we found that oxidation treatments decreased the amplitude of currents evoked by either the agonist (ACh) or co-applied agonist and modulator (ACh + Mor), by as much as 51%, consistent with the introduced bond decreasing channel efficacy. Reduction treatment increased evoked currents up to 89%. The magnitude of the oxidation effects depended on whether agonists were present during oxidation and on the cysteine pair. Additionally, the cysteine mutations themselves decreased Mor potentiation, implicating these residues in modulation. Our findings suggest that these β sheets in the α3 subunit move with respect to each other during activation and modulation, and the residues studied highlight the contribution of this intramolecular allosteric pathway to receptor function. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Neurocognitive predictors of substance use disorders and nicotine dependence in ADHD probands, their unaffected siblings, and controls : a 4-year prospective follow-up

    NARCIS (Netherlands)

    Groenman, Annabeth P.; Oosterlaan, Jaap; Greven, Corina U.; Vuijk, Pieter Jelle; Rommelse, Nanda; Franke, Barbara; Hartman, Catharina A.; Hoekstra, Pieter J.; Sergeant, Joseph; Faraone, Stephen V.; Buitelaar, Jan

    BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a risk factor for substance use disorders (SUDs) and nicotine dependence (ND). Neurocognitive deficits may predict the increased risk of developing SUDs and nicotine dependence. MethodsThis study comprised three groups derived from the

  16. Nicotine transport in lung and non-lung epithelial cells.

    Science.gov (United States)

    Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

    2017-11-01

    Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H

    2010-01-01

    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions......, as measured by c-Fos immunoreactivity, a marker of neuronal activation. Selective depletion of these cholinergic neurons abolishes the SSR180711-induced activation of the mPFC but not the ACCshell, demonstrating their critical importance for alpha(7) nAChR-dependent activation of the mPFC. Contrarily......, selective depletion of dopaminergic neurons in the ventral tegmental area abolishes the SSR180711-induced activation of the ACCshell but not the mPFC or HDB. These results demonstrate 2 distinct neural pathways activated by SSR180711. The BF and mPFC are important for attentional function and may subserve...

  18. Nicotine-dependence-varying effects of smoking events on momentary mood changes among adolescents.

    Science.gov (United States)

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

    2015-02-01

    Theories of nicotine addiction emphasize the initial role of positive reinforcement in the development of regular smoking behavior, and the role of negative reinforcement at later stages. These theories are tested here by examining the effects of amount smoked per smoking event on smoking-related mood changes, and how nicotine dependence (ND) moderates this effect. The current study examines these questions within a sample of light adolescent smokers drawn from the metropolitan Chicago area (N=151, 55.6% female, mean 17.7years). Ecological momentary assessment data were collected via handheld computers, and additional variables were drawn from a traditional questionnaire. Effects of the amount smoked per event on changes in positive affect (PA) and negative affect (NA) after vs. before smoking were examined, while controlling for subject-averaged amount smoked, age, gender, and day of week. ND-varying effects were examined using varying effect models to elucidate their change across levels of ND. The effect of the amount smoked per event was significantly associated with an increase in PA among adolescents with low-to-moderate levels of ND, and was not significant at high ND. Conversely, the effect of the amount smoked was significantly associated with a decrease in NA only for adolescents with low levels of ND. These findings support the role of positive reinforcement in early stages of dependent smoking, but do not support the role of negative reinforcement beyond early stages of smoking. Other potential contributing factors to the relationship between smoking behavior and PA/NA change are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shakir D Alsharari

    Full Text Available Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c. for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of α4 and β2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in β2 and α4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of β2 and α4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile.

  20. Reinforcing effectiveness of nicotine in nonhuman primates: Effects of nicotine dose and history of nicotine self-administration

    Science.gov (United States)

    Kohut, Stephen J.; Bergman, Jack

    2016-01-01

    Rationale Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. Objectives A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in non-human primates. Methods Adult rhesus macaques (N=6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed ratio (FR) 1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1-g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. Results IV nicotine self-administration followed an inverted-U shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that the demand elasticity for nicotine was: 1) dose-dependent and lowest for 0.0032 mg/kg/inj); 2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and 3) decreased after 8 months of daily nicotine self-administration. Conclusions These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited, and may increase over time. PMID:27076210

  1. a2* Nicotinic Acetylcholine Receptors Influence Hippocampus-Dependent Learning and Memory in Adolescent Mice

    Science.gov (United States)

    Lotfipour, Shahrdad; Mojica, Celina; Nakauchi, Sakura; Lipovsek, Marcela; Silverstein, Sarah; Cushman, Jesse; Tirtorahardjo, James; Poulos, Andrew; Elgoyhen, Ana Belén; Sumikawa, Katumi; Fanselow, Michael S.; Boulter, Jim

    2017-01-01

    The absence of a2* nicotinic acetylcholine receptors (nAChRs) in oriens lacunosum moleculare (OLM) GABAergic interneurons ablate the facilitation of nicotine-induced hippocampal CA1 long-term potentiation and impair memory. The current study delineated whether genetic mutations of a2* nAChRs ("Chrna2"[superscript L9'S/L9'S] and…

  2. Gamma-aminobutyric acid mediates nicotine biosynthesis in tobacco under flooding stress

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2016-02-01

    Full Text Available Gamma-aminobutyric acid (GABA is a four-carbon non-protein amino acid conserved from bacteria to plants and vertebrates. Increasing evidence supports a regulatory role for GABA in plant development and the plant's response to environmental stress. The biosynthesis of nicotine, the main economically important metabolite in tobacco, is tightly regulated. GABA has not hitherto been reported to function in nicotine biosynthesis. Here we report that water flooding treatment (hypoxia markedly induced the accumulation of GABA and stimulated nicotine biosynthesis. Suppressing GABA accumulation by treatment with glutamate decarboxylase inhibitor impaired flooding-induced nicotine biosynthesis, while exogenous GABA application directly induced nicotine biosynthesis. Based on these results, we propose that GABA triggers nicotine biosynthesis in tobacco seedlings subjected to flooding. Our results provide insight into the molecular mechanism of nicotine biosynthesis in tobacco plants exposed to environmental stress.

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

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

    2015-01-01

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

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

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

    2015-01-01

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

  5. Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

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    Cross, Sarah J; Lotfipour, Shahrdad; Leslie, Frances M

    2017-03-01

    Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

  6. Relationships Between Craving Beliefs and Abstinence Self-Efficacy are Mediated by Smoking Motives and Moderated by Nicotine Dependence.

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    Reese, Elizabeth D; Veilleux, Jennifer C

    2016-01-01

    Decreased abstinence self-efficacy is linked to increased craving and negative affect, as well as poorer smoking outcomes, such as lapse, relapse, and withdrawal symptom severity. Research suggests that beliefs and cognitions concerning ourselves and the world orient us toward specific goals and thus impact our judgments and behavior. This study serves to investigate whether motives for smoking mediate the relationship between beliefs about craving and abstinence self-efficacy judgments and whether this may differ by nicotine dependence. In a sample of 198 smokers (M age = 34.96, 51.8% female, 81.8% Caucasian), self-report measures of craving beliefs, situational abstinence self-efficacy, and smoking motives were measured. We examined the effect of beliefs on abstinence self-efficacy in both craving and negative affect situations, with craving and negative reinforcement smoking motives as mediators, and nicotine dependence as a moderator. Results indicate that craving beliefs predict lower abstinence self-efficacy judgments in craving situations indirectly through increased craving motives. However, this relationship was only significant for less dependent smokers. Additionally, regardless of nicotine dependence, craving beliefs predicted lower abstinence self-efficacy in negative affect situations via increased negative reinforcement smoking motives. These findings suggest that beliefs concerning the specific nature of craving correlate with smoking motives (ie, smoking goals) and thus abstinence self-efficacy judgments. Furthermore, these associations are stronger for less dependent smokers. Such findings suggest the importance of addressing craving beliefs during smoking cessation treatment, especially for less dependent smokers whose craving beliefs are associated with abstinence self-efficacy across multiple situations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved

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

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    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

  8. Inter-relationships Linking Probability of Becoming a Case of Nicotine Dependence With Frequency of Tobacco Cigarette Smoking.

    Science.gov (United States)

    Vsevolozhskaya, Olga A; Anthony, James C

    2016-12-01

    Once smoking starts, some tobacco cigarette smokers (TCS) can make very rapid transitions into tobacco dependence syndromes (TCD). With adjustment for smoking frequency, we posit female excess risk for this rapid-onset TCD. In a novel application of functional analysis for tobacco research, we estimate four Hill function parameters and plot TCD risk against a gradient of smoking frequency, as observed quite soon after smoking onset. In aggregate, the National Surveys of Drug Use and Health, 2004-2013, identified 1546 newly incident TCS in cross-sectional research, each with standardized TCD assessment. Hill function estimates contradict our apparently over-simplistic hypothesis. Among newly incident TCS males with only 1-3 recent smoking days, an estimated 1%-3% had become rapid-onset TCD cases; non-overlapping confidence intervals show lower TCD risk for females. In contrast, among daily smokers, closer to 50% of female TCS showed rapid-onset TCD, versus under 20% of male TCS, but a larger sample will be needed to confirm the apparent female excess risk at the daily smoking frequency level. Smoking frequency and TCD onset become inter-dependent quite soon after TCS onset. Feedback loops are expected, and might explain a potential reversal of male-female differences across smoking frequency gradients. These novel epidemiological estimates prompt new thinking and questions about interventions. In this large sample epidemiological study, with a nationally representative sample of newly incident TCS assessed cross-sectionally, we see a quite rapid onset of tobacco dependence, with an early male excess that fades out at higher levels of smoking frequency. Next steps include development of outreach and intervention for this very rapid-onset tobacco dependence. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents.

    Directory of Open Access Journals (Sweden)

    Jennifer O'Loughlin

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

  10. Perceived parental care during childhood, ACTH, cortisol and nicotine dependence in the adult.

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    Gerra, Gilberto; Manfredini, Matteo; Somaini, Lorenzo; Milano, Giulia; Ciccocioppo, Roberto; Donnini, Claudia

    2016-11-30

    Studies evidenced the relationship between adverse childhood experiences (ACEs) and tobacco smoking in adulthood. An appropriate parenting style has been found to be associated with children's less frequent tobacco consumption. Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity could represent the potential link between ACEs, mood disorders and smoking susceptibility. We studied a sample of 50 male smokers, affected by nicotine dependence and 50 controls who never smoked. Self-reported retrospective perception of neglect (Child Experience of Care and Abuse: CECA-Q questionnaire), age of smoking onset, number of cigarette/day, psychiatric symptoms (Symptoms Check List 90 scale: SCL 90) and basal level of ACTH and cortisol have been evaluated. Total SCL-90 scores, CECA-Q values and cortisol plasma level were significantly higher among smokers. Cortisol and ACTH values showed a significant direct correlation with CECA-Q and SCL90 total score and an inverse significant correlation with the age of smoking. Cortisol and ACTH did not correlate with the number of cigarette smoked. Once controlled for SCL90 and CECA-Q with multiple regression measures, the association between smoking and hormone levels reversed, suggesting that increased cortisol and ACTH basal levels were attributable to preexisting conditions such as early-life exposure to emotional neglect, psychological problems and a predisposition to addictive behavior. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Association between nicotine dependence and sleeping disorders in patients of an urban emergency department

    OpenAIRE

    Trenkner, Hannah Meike

    2010-01-01

    Previous research on smoking and sleeping disorders suggests that smokers suffer from increased sleeping disorders. The correlation between the degree of nicotin addiction and the presence of sleeping disorders had not been evaluated yet. The presented work aims to determine the association of sleeping disorders with the degree of nicotin addiction. This evaluation is based on data of the "Tobacco Control in an Urban Emergency Department" inquiry that was collected in the context of a randomi...

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

    Science.gov (United States)

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

    2014-06-01

    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. 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. 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). 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

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

    2015-12-30

    Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Passion flower extract antagonizes the expression of nicotine locomotor sensitization in rats.

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    Breivogel, Chris; Jamerson, Brenda

    2012-10-01

    Nicotine, a bioactive component of tobacco, is highly addictive. Numerous therapies have been developed or are currently under investigation for smoking cessation, and all have met with limited success and/or side effects, indicating the need for additional therapies. This study examines the ability of a commerically-available aqueous extract of Passiflora incarnata Linn. (Passifloraceae) to ameliorate the signs of nicotine sensitization using a rat model. Rats were administered 0.4 mg/kg nicotine or vehicle once a day for four consecutive days. Nicotine adminstration produces sensitization of locomotor activity, a phenomenon implicated in the development of nicotine dependence. On the fifth day, locomotor activity of the subjects was monitored as rats from each treatment group were administered 800 mg/kg of Passiflora incarnata extract (or its vehicle) followed by a challenge dose of 0.4 mg/kg nicotine. When given to rats sensitized to nicotine for 4 days, the challenge dose of nicotine increased locomotor activity by more than 2-fold over activity following nicotine challenge in rats treated with vehicle during the sensitization phase. The difference was significant from 15-40 min after nicotine administration. Rats sensitized to nicotine then treated with Passiflora incarnata extract prior to the nicotine challenge exhibited a level of locomotor activity the same as the vehicle-treated controls. Passiflora incarnata extract did antagonize the expression of nicotine locomotor sensitization. Passiflora incarnata extract should be examined in future studies to evaluate its potential for treating nicotine addiction in humans.

  16. Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

    Science.gov (United States)

    Grieder, Taryn E.; George, Olivier; Tan, Huibing; George, Susan R.; Le Foll, Bernard; Laviolette, Steven R.; van der Kooy, Derek

    2012-01-01

    Nicotine, the main psychoactive ingredient of tobacco smoke, induces negative motivational symptoms during withdrawal that contribute to relapse in dependent individuals. The neurobiological mechanisms underlying how the brain signals nicotine withdrawal remain poorly understood. Using electrophysiological, genetic, pharmacological, and behavioral methods, we demonstrate that tonic but not phasic activity is reduced during nicotine withdrawal in ventral tegmental area dopamine (DA) neurons, and that this pattern of signaling acts through DA D2 and adenosine A2A, but not DA D1, receptors. Selective blockade of phasic DA activity prevents the expression of conditioned place aversions to a single injection of nicotine in nondependent mice, but not to withdrawal from chronic nicotine in dependent mice, suggesting a shift from phasic to tonic dopaminergic mediation of the conditioned motivational response in nicotine dependent and withdrawn animals. Either increasing or decreasing activity at D2 or A2A receptors prevents the aversive motivational response to withdrawal from chronic nicotine, but not to acute nicotine. Modification of D1 receptor activity prevents the aversive response to acute nicotine, but not to nicotine withdrawal. This double dissociation demonstrates that the specific pattern of tonic DA activity at D2 receptors is a key mechanism in signaling the motivational effects experienced during nicotine withdrawal, and may represent a unique target for therapeutic treatments for nicotine addiction. PMID:22308372

  17. Performance monitoring in nicotine dependence: Considering integration of recent reinforcement history.

    Science.gov (United States)

    Butler, Kevin; Rusted, Jennifer; Gard, Paul; Jackson, Anne

    2017-05-01

    Impaired monitoring of errors and conflict (performance monitoring; PM) is well documented in substance dependence (SD) including nicotine dependence and may contribute to continued drug use. Contemporary models of PM and complementary behavioural evidence suggest that PM works by integrating recent reinforcement history rather than evaluating individual behaviours. Despite this, studies of PM in SD have typically used indices derived from reaction to task error or conflict on individual trials. Consequently impaired integration of reinforcement history during action selection tasks requiring behavioural control in SD populations has been underexplored. A reinforcement learning task assessed the ability of abstinent, satiated, former and never smokers (N=60) to integrate recent reinforcement history alongside a more typical behavioural index of PM reflecting the degree of reaction time slowing following an error (post-punishment slowing; PPS). On both indices there was a consistent pattern in PM data: Former smokers had the greatest and satiated smokers the poorest PM. Specifically satiated smokers had poorer reinforcement integration than former (p=0.005) and never smokers (p=0.041) and had less post-punishment slowing than former (preinforcement history metric. The concordance of the reinforcement integration and PPS data suggest that this could be a promising method to interrogate PM in future studies. PM is influenced by smoking status. As PM is associated with adapting behaviour, poor PM in satiated smokers may contribute towards continued smoking despite negative consequences. Former smokers show elevated PM suggesting this may be a good relapse prevention target for individuals struggling to remain abstinent however prospective and intervention studies are needed. A better understanding of PM deficits in terms of reinforcement integration failure may stimulate development of novel treatment approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Nicotine Addiction

    NARCIS (Netherlands)

    Andel I van; Rambali AB; Amsterdam JGC van; Wolterink G; Aerts LAGJM van; Vleeming W; TOX; SIR; BMT

    2003-01-01

    This report discusses the current knowledge on nicotine dependence, devoting a special chapter to smoking among youths, given that most smoking careers start in adolescence. The transition period, in which youths go from elementary to high school (ages 13-14), showes to be particularly risky for

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

    Science.gov (United States)

    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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Elevated risk of nicotine dependence among sib-pairs discordant for maternal smoking during pregnancy: evidence from a 40-year longitudinal study.

    Science.gov (United States)

    Shenassa, Edmond D; Papandonatos, George D; Rogers, Michelle L; Buka, Stephen L

    2015-05-01

    Compelling evidence links maternal smoking during pregnancy with elevated risk of nicotine dependence among the offspring. However, no study to date has examined the maternal smoking during pregnancy-nicotine dependence link among sibling-pairs discordant for maternal smoking during pregnancy. We tested two hypotheses that, if supported, suggest that the maternal smoking during pregnancy-nicotine dependence link may be physiologically mediated. Study participants were adult offspring of women enrolled in the Providence and Boston sites of the Collaborative Perinatal Project (1959-1966). Approximately 10% of these adult offspring (average age: 39.6 years) were enrolled in the New England Family Study (n = 1,783), a follow-up study that oversampled families with multiple siblings. Logistic regression models predicting maternal smoking during pregnancy risk on various prospectively collected smoking and marijuana use outcomes, including nicotine dependence, were fit using models that allowed between-mother effects of maternal smoking during pregnancy exposure to differ from within-mother effects. In the absence of significant effect heterogeneity, we calculated a combined estimate. Maternal smoking during pregnancy predicted progression from weekly smoking to nicotine dependence (odds ratio = 1.4 [95% confidence interval = 1.2, 1.8]), but not weekly smoking or progression to marijuana dependence. Current evidence from sibling-pairs discordant for maternal smoking during pregnancy is consistent with previous reports of a dose-response association between maternal smoking during pregnancy and nicotine dependence, as well as of up-regulation of nicotine receptors among animals exposed to maternal smoking during pregnancy. Together, they provide support for the existence of a physiologically mediated link between maternal smoking during pregnancy and nicotine dependence.

  1. SNP rs16969968 as a Strong Predictor of Nicotine Dependence and Lung Cancer Risk in a North Indian Population

    Science.gov (United States)

    Pandey, Namita; Pal, Soumyadip; Sharma, Lokesh Kumar; Guleria, Randeep; Mohan, Anant; Srivastava, Tapasya

    2017-01-01

    Background: The 15q24-25 loci contain genes (CHRNA5 and CHRNA3) encoding nicotinic acetylcholine receptor subunits. We here determined for the first time the association of genetic variants rs16969968 and rs3743074 in CHRNA5 and CHRNA3, respectively, on nicotine dependence and lung cancer risk in a North Indian population by a case-control approach. Methods: Venous blood samples were obtained from 324 participants (108 lung cancer patients and 216 healthy individuals). DNA was extracted and PCR amplified with primers flanking the SNPs rs16969968 and rs3743074. Amplicons were subjected to sequencing and logistic regression was used to analyze association between variables. Results: The risk variant SNP rs16969968 in both heterozygous and homozygous forms appeared to exert a significant effect on nicotine dependence [GA (OR=2.77) and AA (OR=2.53)]. As expected, smoking was strongly associated with lung cancer (OR= 2.62). Risk allele rs16969968 in CHRNA5 also showed a significant association with increased lung cancer risk in our cohort, alone (OR= 4.99) and with smoking as a co-variable (OR= 4.28). Comparison of our analysis with other populations suggested that individuals with rs16969968 risk allele in the Indian population are more susceptible to lung cancer. Conclusion: Overall, the results strongly indicated that, in our cohort North Indian population, the genetic variant rs16969968, but not rs3743074, is significantly associated with both nicotine dependence and increased risk of lung cancer. While the results are significant, there is further need to increase the sample size and improve precision of our risk prediction. PMID:29172281

  2. High reinforcing efficacy of nicotine in non-human primates.

    Directory of Open Access Journals (Sweden)

    Bernard Le Foll

    Full Text Available Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule or increased progressively with successive injections during the session (progressive-ratio schedule, allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys' behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence.

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

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

    2015-01-01

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

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

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    Kassel, Jon D.

    2000-01-01

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

  5. [The assessment of the dependence between antigen CA 125 and nicotinism in patients with benign ovarian tumors including endometrial cysts].

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    Posadzka, Ewa; Jach, Robert; Babczyk, Dorota; Knafel, Anna; Pityński, Kazimierz

    2014-01-01

    Cancer antigen CA-125 is a marker that is primarily used to differentiate benign from malignant tumors as well as to monitor response to ovarian cancer treatment. Taken as a separate marker, it displays low sensitivity and specificity in ovarian cancer diagnosis; however, in combination with other markers it may be successfully applied especially in postmenopausal women. Elevated CA-125 levels in blood serum indicate cancerous as well as non-cancerous diseases. Research aiming to determine environmental factors that may have influence on antigen CA-125 level, and thus on the assessment of this marker's application in gynecological and oncological diseases continues. the aim of the present research is an attempt to estimate the influence of nicotinism on antigen CA-125 in blood serum in patients with diagnosed benign ovarian tumors including endometrial cysts. 174 women aged 16-85 years with diagnosed benign ovarian tumor were qualified for the study. In all patients level of antigen CA-125 in blood serum was assessed preoperatively and nicotinism history was taken. Also transvaginal ultrasound was performed to obtain preliminary diagnosis. Smoking and non-smoking patients were classified into two groups, namely of those with histopathologically confirmed cysts of endometrial type and those with non-endometrial benign ovarian tumors. statistical analysis did not prove any dependence between the CS-125 antigen level and nicotinism in any of these groups. Also additional analysis with division into premenopausal and postmenopausal patients did not determine any statistically significant dependence. Nicotinism does not significantly influence the CA-125 antigen level in patients with benign However, the connection between the addiction severity and its influence on antigen CA-125 in blood serum cannot be excluded. ovarian tumors or endometrial cysts.

  6. Measures and predictors of varenicline adherence in the treatment of nicotine dependence.

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    Peng, Annie R; Morales, Mark; Wileyto, E Paul; Hawk, Larry W; Cinciripini, Paul; George, Tony P; Benowitz, Neal L; Nollen, Nicole L; Lerman, Caryn; Tyndale, Rachel F; Schnoll, Robert

    2017-12-01

    While adherence to medication in smoking cessation clinical trials is strongly associated with clinical outcome, very few studies have evaluated the validity of pill count as a measure of adherence relative to a biological assay, and evaluated a broad range of correlates of adherence. In a smoking cessation clinical trial of varenicline, we compared pill counts collected over 4 different time periods to varenicline salivary levels taken after 2weeks of treatment, as well as evaluated predictors of adherence to varenicline. Using a binary measure of adherence based on salivary varenicline levels, adherence was higher among older, white, and more educated participants. Relative to 3, 7, and 14-day pill count, 12-week pill count was the only significant measure able to discriminate adherence as defined by salivary varenicline levels (assessed by area under the receiver operating characteristic curve; AUC=0.59, p=0.004). Seventy-two percent of participants who indicated adherence on 12-week pill count were classified as adherent based on varenicline saliva levels (sensitivity=0.80; specificity=0.40). There was modest variability in the relationship between 12-week pill count and varenicline levels across race and rate of nicotine metabolism. Lastly, General Estimating Equation models demonstrated that longitudinal changes in withdrawal, craving, negative and positive affect, and side effect count and severity were not related to adherence based on salivary varenicline levels. These results indicate that 12-week pill count was the best, albeit a relatively weak, measure of varenicline adherence; additional factors associated with treatment adherence need to be identified. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

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    Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

    2015-01-01

    Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

  8. Association Between Smoking, Nicotine Dependence, and BDNF Val(66)Met Polymorphism with BDNF Concentrations in Serum

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    Jamal, Mumtaz; Van der Does, Willem; Elzinga, Bernet M.; Molendijk, Marc L.; Penninx, Brenda W. J. H.

    Introduction: Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers,

  9. Nicotine Vapor Inhalation Escalates Nicotine Self-Administration

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

    2015-01-01

    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-hr operant sessions, then exposed to chronic intermittent (12 hrs/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hrs withdrawal. Rats were tested intermittently on days 1, 3 and 5 of the vapor exposure procedure, then tested on consecutive days 6-15 of nicotine vapor exposure. 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 (~3x 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 hrs 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 & 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. PMID:23240929

  10. Nicotine vapor inhalation escalates nicotine self-administration.

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    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. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  11. Acute effects of nicotine amplify accumbal neural responses during nicotine-taking behavior and nicotine-paired environmental cues.

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    Karine Guillem

    Full Text Available Nicotine self-administration (SA is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine. During SA sessions each press of a lever was followed by an intravenous infusion of nicotine (30 µg/kg paired with a combined light-tone cue. Extracellular recordings of single-neuron activity showed that 20% of neurons exhibited a phasic change in firing during the nicotine-directed operant, the light-tone cue, or both. The phasic change in firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons additionally or alternatively showed a sustained decrease in average firing during the SA session relative to a presession baseline period. These session decreases in firing were significantly less prevalent in a group of neurons that were activated during either the operant or the cue than in a group of neurons that were nonresponsive during those events (referred to as task-activated and task-nonactivated neurons, respectively. Moreover, the session decrease in firing was dose-dependent for only the task-nonactivated neurons. The data of the present investigation provide supportive correlational evidence for two hypotheses: (1 excitatory neurophysiological mechanisms mediate the NAc role in cue-maintenance of nicotine SA, and (2 a differential nicotine-induced inhibition of task-activated and task-nonactivated neurons mediates the NAc role in nicotine-induced amplification of cue effects on nicotine SA.

  12. Nicotine promotes vascular endothelial growth factor secretion by human trophoblast cells under hypoxic conditions and improves the proliferation and tube formation capacity of human umbilical endothelial cells.

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    Zhao, Hongbo; Wu, Lanxiang; Wang, Yahui; Zhou, Jiayi; Li, Ruixia; Zhou, Jiabing; Wang, Zehua; Xu, Congjian

    2017-04-01

    Pre-eclampsia, characterized as defective uteroplacental vascularization, remains the major cause of maternal and fetal mortality and morbidity. Previous epidemiological studies demonstrated that cigarette smoking reduced the risk of pre-eclampsia. However, the molecular mechanism remains elusive. In the present study, it is demonstrated that a low dose of nicotine decreased soluble vascular endothelial growth factor receptor 1 (sFlt1) secretion in human trophoblast cells under hypoxic conditions. Nicotine was then observed to promote vascular endothelial growth factor (VEGF) secretion by reducing sFlt1 secretion and increasing VEGF mRNA transcription. Further data showed that nicotine enhanced hypoxia-mediated hypoxia-inducible factor-1α (HIF-1α) expression and HIF-1α small interfering RNA abrogated nicotine-induced VEGF secretion, indicating that HIF-1α may be responsible for nicotine-mediated VEGF transcription under hypoxic conditions. Moreover, conditioned medium from human trophoblast cells treated with nicotine under hypoxic conditions promoted the proliferation and tube formation capacity of human umbilical endothelial cells (HUVEC) by promoting VEGF secretion. These findings indicate that nicotine may promote VEGF secretion in human trophoblast cells under hypoxic conditions by reducing sFlt1 secretion and up-regulating VEGF transcription and improve the proliferation and tube formation of HUVEC cells, which may contribute to elucidate the protective effect of cigarette smoking against pre-eclampsia. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  13. The activity of serum beta-galactosidase in colon cancer patients with a history of alcohol and nicotine dependence: preliminary data

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    Napoleon Waszkiewicz

    2013-08-01

    Full Text Available Introduction: Beta-galactosidase (GAL is a lysosomal exoglycosidase involved in the catabolism of glycoconjugates through the sequential release of beta-linked terminal galactosyl residues. The stimulation of activity of exoglycosidases and other degradative enzymes has been noted in cancers as well as in alcohol and nicotine addiction separately. This is the first study to evaluate the activity of the serum senescence marker GAL in colon cancer patients with a history of alcohol and nicotine dependence, as a potential factor of worse cancer prognosis.Material and Methods: The material was serum of 18 colon cancer patients and 10 healthy volunteers. Ten colon cancer patients met alcohol and nicotine dependence criteria. The activity of beta-galactosidase (pkat/ml was determined by the colorimetric method. Comparisons between groups were made using the Kruskal-Wallis analysis and differences evaluated using the Mann-Whitney U test. Spearman’s rank correlation coefficient was used to measure the statistical dependence between two variables.Results: The activity of serum GAL was significantly higher in colon cancer patients with a history of alcohol and nicotine dependence, in comparison to colon cancer patients without a history of drinking/smoking (p=0.015; 46�0increase, and the controls (p=0.0002; 81�0increase. The activity of serum GAL in colon cancer patients without a history of alcohol/nicotine dependence was higher than the activity in the controls (p = 0.043; 24�0increase.Discussion/Conclusion: Higher activity of beta-galactosidase may potentially reflect the accelerated growth of the cancer, invasion, metastases, and maturation, when alcohol and nicotine dependence coincide with colon cancer. For a better prognosis of colon cancer, alcohol and nicotine withdrawal seems to be required.

  14. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

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    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, such as changes in nicotinic acetylcholine receptor (nAChR) binding, CREB expression, and nicotine metabolism. Age-related differences existed in sensitivity to the effects of acute nicotine, chronic nicotine and nicotine withdrawal on contextual fear conditioning (no changes in cued fear conditioning were seen); younger mice were more sensitive to the acute effects and less sensitive to the effects of nicotine withdrawal 24 hours post treatment cessation. Developmental differences in nAChR binding were associated with the effects of nicotine withdrawal on contextual learning. Developmental differences in nicotine metabolism and CREB expression were also observed, but were not related to the effects of nicotine withdrawal on contextual learning 24 hours post treatment. Chronic nicotine exposure during pre-adolescence or adolescence, however, produced long-lasting impairments in contextual learning that were observed during adulthood, whereas adult chronic nicotine exposure did not. These developmental effects could be related to changes in CREB. Overall, there is a developmental shift in the effects of nicotine on hippocampus-dependent learning and developmental exposure to nicotine results in adult cognitive deficits; these changes in cognition may play an important role in the development and maintenance of nicotine addiction. PMID:22521799

  15. Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

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    Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

    2017-06-01

    Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. The alternative five-factor model of personality, nicotine dependence and relapse after treatment for smoking cessation.

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    Nieva, Gemma; Valero, Sergi; Bruguera, Eugeni; Andión, Óscar; Trasovares, M Victoria; Gual, Antoni; Casas, Miquel

    2011-10-01

    Personality is one of several factors that have been related to the initiation, maintenance and cessation of smoking. This paper aims to analyze the relationship between the alternative five-factor model of personality (AFFM), nicotine dependence (ND), nicotine use (NU) and cessation after twelve months of a cognitive-behavioral therapy combined with medication. In this prospective study, a sample of 103 smokers who were taking part in a workplace smoking cessation intervention, answered the Zuckerman-Kuhlman Personality Questionnaire. ND and NU were measured with the Fagerström Test for the Nicotine Dependence (FTND) and the number of cigarettes smoked per day (CPD), respectively. Tobacco cessation was self-reported at twelve months follow-up and biologically confirmed. Results varied according to gender. In men, low scores on Sociability predicted high ND and large number of CPD. In addition, low scores on Sensation Seeking and high scores on Impulsivity predicted also a high smoking rate at baseline. No personality traits were found to explain ND in women, but high Impulsivity-Sensation Seeking and General Activity predicted high CPD. Predictors of cessation also differed by gender. Apart from FTND level, high levels on Impulsivity predicted relapse in males. In women, high levels on Sociability predicted relapse. This model correctly classified two thirds of abstainers and relapsers for men and three fourths for women at 12months. Furthermore an interaction between personality and gender was observed. The AFFM appears to have a substantial power for predicting cessation. Personality assessment when beginning treatment for smoking cessation could allow incorporating strategies to improve outcomes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. TOBACCO DEPENDENCE TREATMENT WITH NICOTINE REPLACEMENT THERAPY AS ONE OF THE METHODS FOR CARDIOVASCULAR DISEASE RISK REDUCTION

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    O. V. Vikhireva

    2005-01-01

    Full Text Available Aim. To investigate efficacy and safety of nicotine chewing gum and inhaler in individuals trying to quit smoking. To assess expected reduction of cardiovascular disease (CVD and total mortality relative risks (RR.Material and methods. In this open, parallel study, 169 relatively healthy male smokers aged 18-60 years were randomly assigned to free choice vs admission of Nicorette gum (2/4 mg or inhaler (10 mg. At baseline, all participants smoked ≥15 cig/d, for ≥3 years. The intervention phase lasted 3 months; follow-up evaluations were made at 3, 6 and 12 months after nicotine replacement therapy (NRT initiation.Results. Twelve-month results were obtained for 152 subjects (response rate 89.9%. Point prevalence abstinence and reduction (smoking ≤50% of basic daily cigarette amount rates were 19.7% and 35.5%, respectively. Neither abstinence, nor reduction rates depended on Nicorette form (gum vs inhaler, or on choice vs admission factor. The main predictors of long-term efficacy were nicotine dependence severity and contacts with other smokers.NRT was not associated with negative dynamics in objective health parameters (blood pressure, heart rate, ECG parameters, body weight, and body mass index or self-evaluation of health. Both Nicorette forms seemed to be safe and well-tolerated.At 12 months, the expected mean RR reduction for CVD mortality reached 19%, for total mortality – 21%.Conclusion. In Russian clinical settings, NRT efficacy and safety are similar to that demonstrated in numerous international trials. NRT can be recommended as one of the methods of assistance to quit smoking and, therefore, for CVD risk reduction.

  18. Nicotine Gum

    Science.gov (United States)

    Nicotine chewing gum is used to help people stop smoking cigarettes. Nicotine chewing gum should be used together with a ... support groups, counseling, or specific behavioral change techniques. Nicotine gum is in a class of medications called ...

  19. Nicotine Lozenges

    Science.gov (United States)

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

  20. Nicotine dependence and cost-effectiveness of individualized support for smoking cessation: evidence from practice at a worksite in Japan.

    Science.gov (United States)

    Nakamura, Koshi; Sakurai, Masaru; Miura, Katsuyuki; Morikawa, Yuko; Nagasawa, Shin-ya; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki

    2013-01-01

    Given the lack of economic studies evaluating the outcomes of smoking cessation programs from the viewpoint of program sponsors, we conducted a case study to provide relevant information for worksites. The present study was carried out between 2006 and 2008 at a manufacturing factory in the Toyama Prefecture of Japan and included subjects who voluntarily entered a smoking cessation program. The program included face-to-face counselling followed by weekly contact to provide encouragement over six months using e-mail or inter-office mail. Nicotine patches were available if required. All 151 participants stopped smoking immediately. Over the 24-month study period, self-report showed 49.7% abstained continuously from smoking. The rate of 24-month consecutive abstinence was higher in participants with lower Fagerström Test scores for Nicotine Dependence at baseline than in those with higher scores (63.6% for 0-2 points vs. 46.5% for 3-6 points vs. 43.8% for 7-10 points; chi-square test p = 0.19). A logistic regression model showed a significant linear trend for the association between the score and abstinence status after adjustment for possible confounding factors (p = 0.03). The crude incremental cost for one individual to successfully quit smoking due to the support program was ¥46,379 (i.e., ¥100 = $1.28, £0.83, or €1.03 at foreign exchange rates). The corresponding costs for the three categories of the Fagerström Test score for Nicotine Dependence were ¥31,953, ¥47,450 and ¥64,956, respectively. When a sensitivity analysis was conducted based on the 95% confidence interval of the success rate, the variance in the corresponding costs was ¥25,514-45,034 for 0-2 points, ¥38,344-61,824 for 3-6 points, and ¥45,698-108,260 for 7-10 points. The degree of nicotine dependence may therefore be an important determinant of the cost-effectiveness of smoking cessation programs.

  1. Reward, addiction, withdrawal to nicotine.

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    De Biasi, Mariella; Dani, John A

    2011-01-01

    Nicotine is the principal addictive component that drives continued tobacco use despite users' knowledge of the harmful consequences. The initiation of addiction involves the mesocorticolimbic dopamine system, which contributes to the processing of rewarding sensory stimuli during the overall shaping of successful behaviors. Acting mainly through nicotinic receptors containing the α4 and β2 subunits, often in combination with the α6 subunit, nicotine increases the firing rate and the phasic bursts by midbrain dopamine neurons. Neuroadaptations arise during chronic exposure to nicotine, producing an altered brain condition that requires the continued presence of nicotine to be maintained. When nicotine is removed, a withdrawal syndrome develops. The expression of somatic withdrawal symptoms depends mainly on the α5, α2, and β4 (and likely α3) nicotinic subunits involving the epithalamic habenular complex and its targets. Thus, nicotine taps into diverse neural systems and an array of nicotinic acetylcholine receptor (nAChR) subtypes to influence reward, addiction, and withdrawal.

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

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    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 (Pnicotine alone (0.001–0.1 mg/kg/inj; Pnicotine (0.001 or 0.0032 mg/kg/inj)+cocaine combinations (0.0032 mg/kg/inj; Pnicotine alone and nicotine+cocaine polydrug combinations in a nonhuman primate model of drug self-administration. PMID:23337868

  3. Thermochemical Properties of Nicotine Salts

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    Riggs DM

    2014-12-01

    Full Text Available The thermal gravimetric analysis (TGA and differential scanning calorimetry (DSC results presented in this report clearly show that the thermal stability and the endothermic peak nicotine release temperatures are different for different nicotine salts and these temperatures appear to be linked to the general microstructural details of the salt itself. In addition, the peak nicotine release temperatures are highly dependent upon the sample size used. The heat of vaporization for neat (non-protonated nicotine is also sample-size dependent. The TGA data showed that the least stable of the salts tested at elevated temperatures was the liquid salt nicotine triacetate followed by the crystalline materials (e.g., nicotine gallate and finally, the amorphous salts (e.g., nicotine alginate. The DSC results revealed that the liquid and crystalline salts exhibit nicotine release endotherms that are strongly related to the sample weight being tested. The amorphous salts show nicotine endotherm peak temperatures that are nearly independent of the sample weight. The range of peak nicotine release temperatures varied depending upon the specific salts and the sample size from 83 oC to well over 200 oC. Based on these results, the evolution of nicotine from the nicotine salt should be expected to vary based on the composition of the salt, the details of its microstructure, and the amount of nicotine salt tested.

  4. Neurocognitive Insights in Nicotine Addiction

    NARCIS (Netherlands)

    M. Luijten (Maartje)

    2012-01-01

    textabstractIn the Netherlands, 27% of the population is currently smoking. Nicotine is among the most addictive substances of abuse. Thirty-two percent of the people who tried smoking develop nicotine dependence within ten year. This percentage is higher for nicotine than for other substances of

  5. Interactive effects of morphine and nicotine on memory function depend on the central amygdala cannabinoid CB1 receptor function in rats.

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    Tirgar, Fatemeh; Rezayof, Ameneh; Alijanpour, Sakineh; Yazdanbakhsh, Nima

    2018-03-02

    The present study investigated the possible involvement of the central amygdala (CeA) cannabinoid receptors type-1 (CB1Rs) in the interactive effects of morphine and nicotine on memory formation in a passive avoidance learning task. Our results showed that systemic administration of morphine (3 and 6mg/kg, s.c.) immediately after training phase impaired memory consolidation and induced amnesia. Administration of nicotine (0.3 and 0.6mg/kg, s.c.) before testing phase significantly restored morphine-induced amnesia, suggesting a cross state-dependent learning between morphine and nicotine. The results showed that while the administration of the lower dose of nicotine (0.1mg/kg, s.c.) per se did not induce a significant effect on morphine-induced amnesia, intra-CeA injection of arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor agonist (3 and 4ng/rat), significantly potentiated the nicotine response. Furthermore, the blockade of the CeA cannabinoid CB1 receptors by the injection of AM251 (0.75 and 1ng/rat) reversed the potentiative effect of nicotine (0.6mg/kg, s.c.) on morphine-induced amnesia. It should be considered that bilateral injection of the same doses of ACPA or AM251 (0.5-1ng/rat) into the CeA by itself had no effect on morphine response in a passive avoidance learning task. Confirmed by the cubic interpolation planes, the dose-response data revealed a cross-state-dependent learning between morphine and nicotine which may be mediated by the CeA endocannabinoid system via CB1 receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Nicotine vaccines for smoking cessation-present and future

    Directory of Open Access Journals (Sweden)

    Richa

    2013-01-01

    Full Text Available Background: Worldwide tobacco is the leading cause of preventable death. Anew treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This article aimed to review the mechanism of action, current status of research and future aspects for the development of vaccines against nicotine. Materials & Method: The literature search of publications indexed was carried out in PubMed, Medline, Google scholar databases. Total 25 animal trials, human trials under various phases of clinical trials, unpublished document and cross-sectional survey were reviewed. Results: This immunization will act on immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. Nicotine vaccines are irreversible, provide protection over years and need booster injections. Efficiency of the vaccines is directly related to the antibody levels which help to optimize the vaccine effect. Nicotine vaccines are today in an advanced stage of clinical evaluation trials. Conclusions: Though, nicotine vaccine has considerable therapeutic potential, they do not target the non pharmacological factors that maintain tobacco dependence. So combination of nicotine vaccine with behavioral interventions would be effective mode to motivate abstinence from tobacco use.

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

    Science.gov (United States)

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

    2015-08-15

    Protein kinases can modify the function of many proteins including ion channels. However, the role of protein kinase A in modifying nicotinic receptors in the CNS has never been investigated. We showed through whole-cell recordings of layer 1 prefrontal cortical interneurons that α7 nicotinic responses are negatively modulated by protein kinase A. Furthermore, we show that stimulation of dopamine receptors can similarly attenuate α7 nicotinic responses through the activation of protein kinase A. These results suggest how the interaction of the cholinergic and dopaminergic systems may influence neuronal excitability in the brain. 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

  8. [Characteristics of smoking, nicotine dependence and motivation for change in specialists training in health sciences (residents) in Andalusia (Spain)].

    Science.gov (United States)

    Juárez-Jiménez, M V; Valverde-Bolívar, F J; Pérez-Milena, A; Moreno-Corredor, A

    2015-09-01

    As there are few studies on the smoking habits of specialists training in health sciences (residents), it is of interest to determine the prevalence of smoking, nicotine dependence and motivation for change, and their relationship with other variables (personal, work and consumption of other drugs). A multicentre, cross-sectional study using a questionnaire was conducted in 2012. All the residents who were studying in Teaching Health Centres in Andalusia (Spain) completed a questionnaire, which was sent by e-mail, collecting: age, sex, specialty, country of origin, qualitative-quantitative consumption of tobacco, age of onset/cessation, Fagerström test and stage of change (Proschaka). A total of 2667 residents (63% of total) completed the questionnaire. The mean age was 29.1 years (± 5.2), 69% female, 89% Spanish, and 86% physicians. Of the 17% who smoked (daily pattern-47%, intermittently-41%, related to leisure-3%), starting at 17.4 years (±3.5) and mean of 7.5 cigarettes per day (±7.1), higher medical specialties (P=.067 ANOVA), and in men (P=.074, Student-t). More than three-quarters (82%) had a low nicotine dependence, being higher in hospital medical specialties (P=.078 χ(2)). Of the total, 7% were former smokers, and 48% wanted to quit smoking (contemplation 38%, preparation 10%). In the multivariate analysis there was a link between smoking and alcohol consumption (OR 2.84) and illegal drugs (OR 3.57). There were no differences by age or country. The consumption of tobacco in residents is less than the general population, with a low dependence and better willingness to change. The period of specialised training is a good time to offer tobacco interventions. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  9. An Application of Planned Behavior Theory in Predicting Nicotine Dependence among Water pipe Consumer Women in Bushehr City in 2013-14

    Directory of Open Access Journals (Sweden)

    M Saeed Firoozabadi

    2016-07-01

    Full Text Available Abstract Introduction: Today, water pipe smoking is widespread in the world that can lead to death of million individuals. This study aimed to determine the predictors of nicotine dependence among women water pipe consumers in Bushehr in 2013-2014. Methods: In this cross-sectional (descriptive and analytical study, 430 women water pipe smokers were selected via simple sampling and snowball methods. A structured interview was conducted on 20 women water pipe consumers in order to design a researcher-made questionnaire via appropriate statistical tests. The collected data were analyzed using SPSS statistical software. Results: The overall mean and standard deviation scores for nicotine dependence were 36.73±13.57 and 40.71±12.63, respectively. The highest and the lowest score were related to nicotine dependence and perceived behavioral control, respectively. All constructs explained water pipe dependence behavior except instrumental attitude and subjective norm. In fact, self-efficacy and affective attitude were introduced as the strongest and the weakest predictors respectively. Conclusion: Regarding unfavorable status of nicotine dependence behavior among water pipe consumer women, intervention programs are recommended in order to enhance the self-efficacy in decreasing this behavior, decrease appropriate affection to water pipe and decrease descriptive norm among these women.

  10. Electronic Nicotine Delivery Systems.

    Science.gov (United States)

    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. Copyright © 2015 by the American Academy of Pediatrics.

  11. Does smoking abstinence influence distress tolerance? An experimental study comparing the response to a breath-holding test of smokers under tobacco withdrawal and under nicotine replacement therapy.

    Science.gov (United States)

    Cosci, Fiammetta; Anna Aldi, Giulia; Nardi, Antonio Egidio

    2015-09-30

    Distress tolerance has been operationalized as task persistence in stressful behavioral laboratory tasks. According to the distress tolerance perspective, how an individual responds to discomfort/distress predicts early smoking lapses. This theory seems weakly supported by experimental studies since they are limited in number, show inconsistent results, do not include control conditions. We tested the response to a stressful task in smokers under abstinence and under no abstinence to verify if tobacco abstinence reduces task persistence, thus distress tolerance. A placebo-controlled, double-blind, randomized, cross-over design was used. Twenty smokers underwent a breath holding test after the administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline and directly before and after each challenge. Abstinence induced a statistically significant shorter breath holding duration relative to the nicotine condition. No different response to the breath holding test was observed when nicotine and placebo conditions were compared. No response to the breath holding test was found when pre- and post-test values of heart rate, blood pressure, Visual Analogue Scale for fear or discomfort were compared. In brief, tobacco abstinence reduces breath holding duration but breath holding test does not influence discomfort. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Nicotine dependence as a mediator of Project EX’s effects to reduce tobacco use in scholars

    Directory of Open Access Journals (Sweden)

    María T Gonzálvez

    2016-08-01

    Full Text Available 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 nicotine dependence. 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 ≤.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

  13. The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype.

    Science.gov (United States)

    Csala, Iren; Egervari, Luca; Dome, Peter; Faludi, Gabor; Dome, Balazs; Lazary, Judit

    2015-06-03

    Neuronal nicotinic acetylcholinergic receptors (nAChR) and especially α4β2 nAChRs are the major targets for cessation medications and also for some promising antidepressant agents. Furthermore, depressive symptoms pose multifacet difficulties during cessation therapy. However, gene encoding for the β2 subunit of nAChRs has been poorly investigated in association with depression. Since both nicotine dependence (ND) and depressive phenotype are complex disorders, we investigated the effects of a significant early life experience, maternal bonding style (MB) and CHRNB2 gene SNPs on smoking-related depression. We recruited two hundred and thirty-two treatment-seeking smokers in our study. Phenotypic variants were evaluated using the Fagerstrom Test for Nicotine Dependence (FTND), the Zung Self-Rating Depression Scale (ZSDS) and the Parental Bonding Instrument (PBI). Besides the total score (TS) of ZSDS, impulsivity (ZSDS-I) and suicidal ideation (ZSDS-S) were distinguished as phenotypic variable. DNAs were extracted from buccal mucosa samples and one SNP in promoter and two SNPs in 3' UTR of CHRNB2 gene were genotyped. GLM and ANOVA tests were performed for genotype associations and interaction analyses. Maternal bonding had a significant impact on depressive phenotypes. Low care, high protection and affectionless control (ALC) were associated with ZSDS-TS and all subphenotypes of ZSDS. One SNP, the rs2072660 in 3' UTR, had a significant effect on the FTND score (p=0.010). Direct association of CHRNB2 variants and depressive phenotypes were not significant. However, in interaction with ALC, rs2072660 was significantly associated with ZSDS-S (p=0.005). MB had no significant effect on smoking-related phenotype. Our results highlight the important role of 3' UTR in the CHRNB2 gene in the shared molecular background of ND and depressive phenotype. Parental bonding style can be suggested as a significant environmental factor in further GxE studies of depression. The

  14. Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner.

    Science.gov (United States)

    Caruso, Michael J; Crowley, Nicole A; Reiss, Dana E; Caulfield, Jasmine I; Luscher, Bernhard; Cavigelli, Sonia A; Kamens, Helen M

    2018-03-01

    Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because little is known about the factors underlying this comorbidity, we investigated the effects of adolescent stress on anxiety-like behavior and nicotine responses within individual animals. Adolescent male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS; repeated cycles of social isolation + social reorganization) or control conditions from postnatal days (PND) 25-59. Anxiety-like behavior and social avoidance were measured in the elevated plus-maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144; Experiment 2: 95-97), respectively. Acute nicotine-induced locomotor, hypothermic, corticosterone responses, (Experiment 1: PND 56-59; Experiment 2: PND 65-70) and voluntary oral nicotine consumption (Experiment 1: PND 116-135; Experiment 2: 73-92) were also examined. Finally, we assessed prefrontal cortex (PFC) and nucleus accumbens (NAC) synaptic transmission (PND 64-80); brain regions that are implicated in anxiety and addiction. Mice exposed to adolescent CVSS displayed increased anxiety-like behavior relative to controls. Further, CVSS altered synaptic excitability in PFC and NAC neurons in a sex-specific manner. For males, CVSS decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents in the PFC and NAC, respectively. In females, CVSS decreased the amplitude of spontaneous inhibitory postsynaptic currents in the NAC. Adolescent CVSS did not affect social avoidance or nicotine responses and anxiety-like behavior was not reliably associated with nicotine responses within individual animals. Taken together, complex interactions between PFC and NAC function may contribute to adolescent stress-induced anxiety-like behavior without influencing nicotine responses. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Enhancing effect of menthol on nicotine self-administration in rats

    Science.gov (United States)

    Biswas, Lisa; Harrison, Erin; Gong, Yongzhen; Avusula, Ramachandram; Lee, Jonathan; Zhang, Meiyu; Rousselle, Thomas; Lage, Janice; Liu, Xiu

    2016-01-01

    Rationale Tobacco smoking is a leading preventable cause of premature death in the United States. Menthol is a significant flavoring additive in tobacco products. Clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. However, it is unclear whether menthol enhances the reinforcing actions of nicotine and thus facilitates nicotine consumption. This study employed a rat model of nicotine self-administration to examine the effects of menthol on nicotine-taking behavior. Methods Male Sprague-Dawley rats were trained in daily 1-h sessions to press a lever for intravenous nicotine self-administration under a fixed-ratio 5 schedule of reinforcement. In separate groups, rats self-administered nicotine at four different doses (0.0075, 0.015, 0.03, and 0.06 mg/kg/infusion). Five minutes prior to the two test sessions, menthol (5 mg/kg) or its vehicle was administered intraperitoneally in all rats in a counterbalanced design within each group. In separate rats that self-administered 0.015 mg/kg/infusion nicotine, menthol dose-response function was determined. Menthol was also tested on food self-administration. Results An inverted U-shaped nicotine dose-response curve was observed. Menthol pretreatment shifted the nicotine dose-response curve to the left. The facilitating effect of menthol on the self-administration of 0.015 mg/kg/infusion nicotine was dose-dependent, whereas it produced similar effects at doses above the threshold of 2.5 mg/kg. Menthol tended to suppress the self-administration of food pellets. Conclusions These data demonstrate that menthol enhances the reinforcing effects of nicotine, and the effect of menthol was specific to nicotine. The findings suggest that menthol directly facilitates nicotine consumption, thereby contributing to tobacco smoking. PMID:27473365

  16. Métodos para abandono do tabagismo e tratamento da dependência da nicotina Methods for smoking cessation and treatment of nicotine dependence

    Directory of Open Access Journals (Sweden)

    Aracy Pereira Silveira Balbani

    2005-12-01

    Full Text Available O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC, aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina, e segunda linha (clonidina e nortriptilina. A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO. A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.Smoking is related to 30% of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS, enhances alertness and reduces the appetite. A 50% reduction of nicotine consumption may trigger withdrawal

  17. Motivation and readiness for tobacco cessation among nicotine dependent postmenopausal females: A pilot study.

    Science.gov (United States)

    Peltier, MacKenzie R; Roys, Melanie R; Waters, Aaron F; Vinci, Christine; Waldo, Krystal M; Stewart, Shelby A; Toups, Robert C; Jones, Louis; Copeland, Amy L

    2018-04-01

    Despite considerable health risks due to lower levels of estrogen production and the compounding antiestrogenic effects of nicotine, postmenopausal females continue to smoke. These females face significant barriers to cessation, including negative affect, weight concerns, and menopausal symptom severity. The current pilot study explored the effect of negative affect, weight concerns, and menopausal symptom severity on motivation and readiness to quit smoking. Eighteen postmenopausal smokers were randomized to receive brief motivational interviewing (B-MI; n = 8) or control treatment (i.e., a 1-hour video, n = 10). Participants completed measures of negative affect, weight concerns, and menopausal symptoms, as well as measures of motivation and readiness to quit. Motivation and readiness to quit were reassessed one week following treatment. At baseline, weight concerns, specifically surrounding smoking to prevent overeating, were identified as related to increased motivation to quit smoking. Menopausal symptom severity, specifically somatic symptoms, assessed at baseline, was associated with increased readiness for cessation. B-MI did not increase motivation or readiness to quit; however, results indicate that cigarettes per day decreased from baseline to follow-up by approximately 20-30%. These results provide valuable insight into enhancing engagement in a cessation treatment among this population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  18. The neuronal pathways mediating the behavioral and addictive properties of nicotine.

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    Balfour, David J K

    2009-01-01

    This chapter considers the neurobiological mechanisms that are thought to mediate the reinforcing or rewarding properties of nicotine. It focuses on the data (derived principally from studies with experimental animals) showing that nicotine, like other drugs of dependence, stimulates the mesolimbic dopamine (DA) neurones that project to the nucleus accumbens and that these effects play a pivotal role in the biology underlying nicotine dependence. The reinforcing or rewarding properties of nicotine are thought to be associated particularly with the increase in DA overflow evoked in the shell subdivision of the accumbens. However, behavioural studies suggest that these properties of nicotine in experimental animals do not seem to be sufficiently potent to explain the powerful addiction to tobacco experienced by most habitual smokers. This chapter also considers the biological mechanisms that mediate the effects of cues and stimuli associated with the presentation of nicotine, which are thought to contribute significantly to the powerful addictive properties of tobacco smoke.

  19. Nicotine stimulus expectancy differentially affects reaction time in healthy nonsmokers and smokers depending on sex: a pilot study.

    Science.gov (United States)

    Weimer, Katja; Horing, Björn; Stürmer, Julian; Klosterhalfen, Sibylle; Zipfel, Stephan; Enck, Paul

    2013-06-01

    Effects of nicotine on neurocognitive performance have been shown but are influenced by nonpharmacological expectancies in smokers, whereas there is little knowledge about expectancy effects in nonsmokers. A half balanced placebo design provides no drug but only placebo and tests the effects of expectations elicited by the information that nicotine was given. Sixty-four healthy participants balanced for smoking status and sex were told that a chewing gum may contain either nicotine or is a placebo in a double-blinded and randomized fashion. One hour later and immediately before neurocognitive function testing (Parametric Go/No-Go task) they were informed--balanced for smoking status and sex--that they belong to the nicotine or to the placebo group. Reaction times of Go responses (RT) and the number of false No-Go responses were analyzed. A significant interaction of all three factors (information, smoking status, sex) was found, indicating that the information to have received nicotine compared with placebo shortened RTs in female smokers but increased it in female nonsmokers, whereas results in men are in part reversed. No effects on No-Go errors were found, and beliefs about nicotine effects had no influence on results. Therefore, the known effects of nicotine on RTs could be influenced by stimulus expectancy not only in smokers but also in nonsmokers. Furthermore, previous results on sex-specific responsiveness to nicotine instructions are supported. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  20. Photocatalytic degradation of nicotine in an aqueous solution using unconventional supported catalysts and commercial ZnO/TiO{sub 2} under ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Franco, Marcela Andrea Espina de, E-mail: marcela.eq@gmail.com; Silva, William Leonardo da; Bagnara, Mônica; Lansarin, Marla Azário; Zimnoch dos Santos, João Henrique

    2014-10-01

    Nicotine, a highly toxic alkaloid, has been detected in effluents, surface and groundwater and even bottled mineral water. The present work studied the photocatalytic degradation of nicotine in aqueous solution, under ultraviolet irradiation. The experiments were carried out using commercial (ZnO, TiO{sub 2}) and non-conventional catalysts, which were prepared from industrial and laboratory waste. Two experimental designs (CCD) were performed for both commercial catalysts, and initial nicotine concentration, catalyst concentration and initial solution pH effects were studied. Then, the synthesized catalysts were tested under the optimal conditions which were found through CCDs. Using commercial catalysts, about 98% of the alkaloid was degraded by ZnO, and 88% by TiO{sub 2}, in 1 h. Among the non-conventional catalysts, the highest photocatalytic degradation (44%) was achieved using the catalyst prepared from a petrochemical industry residue. - Highlights: • The photocatalytic degradation of nicotine was studied under UV irradiation. • Commercial catalysts ZnO and TiO{sub 2} were tested using two central composite designs. • Initial nicotine concentration, catalyst concentration and pH were evaluated. • Catalysts were prepared using chemical wastes and tested at the best conditions.

  1. Photocatalytic degradation of nicotine in an aqueous solution using unconventional supported catalysts and commercial ZnO/TiO2 under ultraviolet radiation

    International Nuclear Information System (INIS)

    Franco, Marcela Andrea Espina de; Silva, William Leonardo da; Bagnara, Mônica; Lansarin, Marla Azário; Zimnoch dos Santos, João Henrique

    2014-01-01

    Nicotine, a highly toxic alkaloid, has been detected in effluents, surface and groundwater and even bottled mineral water. The present work studied the photocatalytic degradation of nicotine in aqueous solution, under ultraviolet irradiation. The experiments were carried out using commercial (ZnO, TiO 2 ) and non-conventional catalysts, which were prepared from industrial and laboratory waste. Two experimental designs (CCD) were performed for both commercial catalysts, and initial nicotine concentration, catalyst concentration and initial solution pH effects were studied. Then, the synthesized catalysts were tested under the optimal conditions which were found through CCDs. Using commercial catalysts, about 98% of the alkaloid was degraded by ZnO, and 88% by TiO 2 , in 1 h. Among the non-conventional catalysts, the highest photocatalytic degradation (44%) was achieved using the catalyst prepared from a petrochemical industry residue. - Highlights: • The photocatalytic degradation of nicotine was studied under UV irradiation. • Commercial catalysts ZnO and TiO 2 were tested using two central composite designs. • Initial nicotine concentration, catalyst concentration and pH were evaluated. • Catalysts were prepared using chemical wastes and tested at the best conditions

  2. Nicotine poisoning

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002510.htm Nicotine poisoning To use the sharing features on this page, please enable JavaScript. Nicotine is a bitter-tasting compound that naturally occurs ...

  3. Effects of nicotine in experimental animals and humans: an update on addictive properties.

    Science.gov (United States)

    Le Foll, Bernard; Goldberg, Steven R

    2009-01-01

    Tobacco use through cigarette smoking is the leading preventable cause of death in the developed world. Nicotine, a psychoactive component of tobacco, appears to play a major role in tobacco dependence, but the reinforcing effects of nicotine have often been difficult to demonstrate directly in controlled studies with laboratory animals or human subjects. Here we update our earlier review published in Psychopharmacology (Berl) in 2006 on findings obtained with various procedures developed to study dependence-related behavioral effects of nicotine in experimental animals and humans. Results obtained with drug self-administration, conditioned place preference, subjective reports of nicotine effects and nicotine discrimination indicate that nicotine can function as an effective reinforcer of drug-seeking and drug-taking behavior both in experimental animals and humans under appropriate conditions. Interruption of chronic nicotine exposure produces ratings of drug withdrawal and withdrawal symptoms that may contribute to relapse. Difficulties encountered in demonstrating reinforcing effects of nicotine under some conditions, relative to other drugs of abuse, may be due to weaker primary reinforcing effects of nicotine, to aversive effects produced by nicotine, or to a more critical contribution of environmental stimuli to the maintenance of drug-seeking and drug-taking behavior with nicotine than with other drugs of abuse. Several recent reports suggest that other chemical substances inhaled along with nicotine in tobacco smoke may play a role in sustaining smoking behavior. However, conflicting results have been obtained with mice and rats and these findings have not yet been validated in nonhuman primates or human subjects. Taken together, these findings suggest that nicotine acts as a typical drug of abuse in experimental animals and humans in appropriate situations.

  4. Psychometric evaluation of the Patient-Reported Outcomes Measurement Information System (PROMIS) Nicotine Dependence Item Bank for use with electronic cigarettes.

    Science.gov (United States)

    Morean, Meghan; Krishnan-Sarin, Suchitra; Sussman, Steve; Foulds, Jonathan; Fishbein, Howard; Grana, Rachel; O'Malley, Stephanie S

    2018-01-02

    Psychometrically sound measures of e-cigarette dependence are lacking. We modified the PROMIS Nicotine Dependence Item Banks for use with e-cigarettes and evaluated the psychometrics of the 22-, 8- and 4-item adapted versions. 1009 adults who reported using e-cigarettes at least weekly completed an anonymous survey in Summer 2016 (50.2% male, 77.1% White, mean age 35.81 [10.71], 66.4% daily e-cigarette users, 72.6% current cigarette smokers). Psychometric analyses included confirmatory factor analysis, internal consistency, measurement invariance, examination of mean-level differences, convergent validity, and test-criterion relationships with e-cigarette use outcomes. All PROMIS-E versions had confirmable, internally consistent latent structures that were scalar invariant by sex, race, e-cigarette use (non-daily/daily), e-liquid nicotine content (no/yes), and current cigarette smoking status (no/yes). Daily e-cigarette users, nicotine e-liquid users, and cigarette smokers reported being more dependent on e-cigarettes than their counterparts. All PROMIS-E versions correlated strongly with one another, evidenced convergent validity with the Penn State E-cigarette Dependence Index and time to first e-cigarette use in the morning, and evidenced test-criterion relationships with vaping frequency, e-liquid nicotine concentration, and e-cigarette quit attempts. Similar results were observed when analyses were conducted within subsamples of exclusive e-cigarette users and duals-users of cigarettes and e-cigarettes. Each PROMIS-E version evidenced strong psychometric properties for assessing e-cigarette dependence in adults who either use e-cigarette exclusively or who are dual-users of cigarettes and e-cigarettes. However, results indicated little benefit of the longer versions over the 4-item PROMIS-E, which provides an efficient assessment of e-cigarette dependence. The availability of the novel, psychometrically sound PROMIS-E can further research on a wide range of

  5. Nicotine and tobacco

    Science.gov (United States)

    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

  6. Robust Escalation of Nicotine Intake with Extended Access to Nicotine Self-Administration and Intermittent Periods of Abstinence

    Science.gov (United States)

    Cohen, Ami; Koob, George F; George, Olivier

    2012-01-01

    Although established smokers have a very regular pattern of smoking behavior, converging lines of evidence suggest that the escalation of smoking behavior is a critical factor in the development of dependence. However, the neurobiological mechanisms that underlie the escalation of smoking are unknown, because there is no animal model of the escalation of nicotine intake. On the basis of the pattern of smoking behavior in humans and presence of monoamine oxidase inhibitors in tobacco smoke, we hypothesized that the escalation of nicotine intake may only occur when animals are given extended-access (21 h per day) self-administration sessions after repeated periods of abstinence (24–48 h), and after chronic inhibition of monoamine oxidase using phenelzine sulfate. Intermittent access (every 24–48 h) to extended nicotine self-administration produced a robust escalation of nicotine intake, associated with increased responding under fixed- and progressive-ratio schedules of reinforcement, and increased somatic signs of withdrawal. The escalation of nicotine intake was not observed in rats with intermittent access to limited (1 h per day) nicotine self-administration or daily access to extended (21 h per day) nicotine self-administration. Moreover, inhibition of monoamine oxidase with daily administration of phenelzine increased nicotine intake by ∼50%. These results demonstrate that the escalation of nicotine intake only occurs in animals given intermittent periods of abstinence with extended access to nicotine, and that inhibition of monoamine oxidase may contribute to the escalation of smoking, thus validating both an animal model of the escalation of smoking behavior and the contribution of monoamine oxidase inhibition to compulsive nicotine-seeking. PMID:22549121

  7. Genetic Background Influences the Effects of Withdrawal from Chronic Nicotine on Learning and High-Affinity Nicotinic Acetylcholine Receptor Binding in the Dorsal and Ventral Hippocampus

    Science.gov (United States)

    Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2013-01-01

    Rationale The effects of nicotine on cognitive processes may play an important role in nicotine addiction. Nicotine withdrawal impairs hippocampus-dependent learning and genetic factors influence this effect. However, the neural changes that contribute to these impairments are unknown. Chronic nicotine upregulates hippocampal nicotinic acetycholine receptors (nAChRs), which may contribute to cognitive deficits when nicotine administration ceases. If nAChR upregulation underlies withdrawal-deficits in learning, then strains of mice exhibiting withdrawal-deficits in hippocampus-dependent learning should also show upregulation of hippocampal nAChRs. Objectives Here, we examined the effects of nicotine withdrawal on fear conditioning and [3H]epibatidine binding in the dorsal and ventral hippocampus in two inbred mouse strains and their F1 hybrids. Methods Male C57BL/6NTac, 129S6/SvEvTac, and B6129SF1/Tac mice were administered chronic nicotine (18 mg/kg/d) for 12 days through osmotic pumps and then were trained and tested in fear conditioning 24 hours after cessation of nicotine treatment. Results Nicotine withdrawal impaired hippocampus-dependent contextual conditioning in C57BL/6NTac mice but not 129S6/SvEvTac or B6129SF1/Tac mice; no changes were observed in hippocampus-independent cued fear conditioning. Upregulated [3H]epibatidine binding was found in the dorsal, but not ventral, hippocampus of C57BL/6NTac mice and in the ventral hippocampus of B6129SF1/Tac mice after chronic nicotine. Conclusions Upregulation of high-affinity binding sites in the dorsal hippocampus of C57BL/6NTac mice, the only strain that exhibited nAChR upregulation in this region and withdrawal-deficits in contextual conditioning, suggests that upregulation of high-affinity binding sites in the dorsal hippocampus mediates, in part, nicotine withdrawal-deficits in contextual conditioning and genetic background modulates these effects. PMID:22836371

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

    Science.gov (United States)

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

    2016-07-01

    Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. © 2015 Society for the Study of Addiction.

  9. Nicotine-induced and D1-receptor-dependent dendritic remodeling in a subset of dorsolateral striatum medium spiny neurons.

    Science.gov (United States)

    Ehlinger, Daniel G; Burke, Julian C; McDonald, Craig G; Smith, Robert F; Bergstrom, Hadley C

    2017-07-25

    Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. Whether MSN dendrites in the dorsal striatum undergo a similar pattern of nicotine-induced structural remodeling is unknown. A morphometric analysis of Golgi-stained MSNs in rat revealed a natural asymmetry in dendritic morphology across the mediolateral axis, with larger, more complex MSNs found in the dorsolateral striatum (DLS). Chronic nicotine produced a lasting (at least 21day) expansion in the dendritic complexity of MSNs in the DLS, but not dorsomedial striatum (DMS). Given prior evidence that MSN subtypes can be distinguished based on dendritic morphology, MSNs were segregated into morphological subpopulations based on the number of primary dendrites. Analysis of these subpopulations revealed that DLS MSNs with more primary dendrites were selectively remodeled by chronic nicotine exposure and remodeling was specific to the distal-most portions of the dendritic arbor. Co-administration of the dopamine D1 receptor (D1R) antagonist SCH23390 completely reversed the selective effects of nicotine on DLS MSN dendrite morphology, supporting a causal role for dopamine signaling at D1 receptors in nicotine-induced dendrite restructuring. Considering the functional importance of the DLS in shaping and expressing habitual behavior, these data support a model in which nicotine induces persistent and selective changes in the circuit connectivity of the DLS that may promote and sustain addiction-related behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Nicotine addiction and treatment.

    Science.gov (United States)

    Rose, J E

    1996-01-01

    The persistence of cigarette smoking despite widespread awareness of adverse health effects results from an underlying addiction to nicotine. Unaided attempts to quit smoking are generally unsuccessful. This article discusses nicotine addition and therapeutic techniques that have been or are being developed to relieve smoking withdrawal symptoms and promote abstinence from smoking. These techniques include nicotine chewing gum, skin patches, nasal sprays, and inhalers, as well as pharmacotherapies such as mecamylamine and clonidine, serotonergic treatments such as buspirone, and antidepressants such as buproprion. A nondrug approach using cigarette substitutes that mimic the airway sensations produced by cigarette smoke is also discussed.

  11. Nicotine increases anterior insula activation to expected and unexpected outcomes among nonsmokers.

    Science.gov (United States)

    Addicott, Merideth A; Oliver, Jason A; Joseph McClernon, F

    2017-04-01

    Tobacco has a higher rate of dependence than other drugs of abuse. However, the psychopharmacological effects of nicotine are incongruent with the tenacity of tobacco addiction since nicotine does not produce robust euphoria in humans or self-administration in rodents. A potential explanation is that nicotine amplifies the salience of other stimuli that have some incentive value, which could influence the initiation and persistence of smoking. However, the neural mechanisms of this process are unknown. One way that nicotine may amplify the salience of other stimuli is by enhancing reward prediction errors. We hypothesized that nicotine would enhance the neural response to unexpected (relative to expected) rewards compared to placebo. Twenty-three nonsmokers underwent two fMRI scans, following nicotine (1 mg) or placebo administration, while performing an outcome expectation task. In the task, a pair of cues was associated with either a subsequent reward (the image of a $100 bill) or a nonreward (the image of a blurry rectangle). On 20% of trials, the cue was followed by an unexpected outcome. Although nicotine did not affect the magnitude of prediction errors relative to placebo, nicotine did increase BOLD activation in the anterior insula/inferior frontal gyrus and decrease activation in the caudate across all outcome types (including both rewards and nonrewards). The insula and caudate could play a role in the initial effects of nicotine in nonsmokers, and these changes in baseline may be the mechanism that underlies how nicotine amplifies the salience of nondrug stimuli.

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

    Science.gov (United States)

    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.

  13. Sub-acute administration of lower doses of nicotine caused sex-dependent improvement of renal function in Wistar rats

    Directory of Open Access Journals (Sweden)

    Ojo Rufus Akomolafe

    Full Text Available The adverse and beneficial health effects of nicotine (NIC, the major alkaloid found in cigarettes and tobacco, are controversial. Most studies on NIC have focused on its effects on cardiovascular and nervous functions. This study aimed at determining dose- and sex-specific effects of sub-acute (28 days NIC administration on some indices of kidney function in Wistar rats. Forty rats (20 males and 20 females, 8–9 weeks old (each housed in separate metabolic cage, were used for this study such that graded doses of NIC (1, 2 and 4 mg/kg i.p. for 28 days were administered to both sexes while each control received distilled water at 0.2 mL/100 g i.p. Blood was collected under ketamine anesthesia (10 mg/kg i.m for analyses and results obtained were compared at p < 0.05. The result showed beneficial alterations in plasma and urine level of creatinine, urea and uric acid (p < 0.05 as well as plasma and urine electrolyte level (Na+ and K+ in both sexes (p < 0.05. Also, there was significant improvement in creatinine clearance (p < 0.05 with no appreciable difference in their histological examination. Although these beneficial effects were more pronounced in the female than in the male (p < 0.05, administration at the highest dose showed potentially deleterious alterations from normal beneficial trend (p < 0.05 in both sexes. It was concluded that sub-acute administration of lower doses of NIC improves kidney function of Wistar rats; an effect that was more pronounced in the females than their male counterparts. Keywords: Nicotine, Wistar rats, Creatinine clearance, Plasma and urine electrolytes, Renal function

  14. Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats.

    Science.gov (United States)

    Feltenstein, Matthew W; Ghee, Shannon M; See, Ronald E

    2012-03-01

    Tobacco addiction is a relapsing disorder that constitutes a substantial worldwide health problem, with evidence suggesting that nicotine and nicotine-associated stimuli play divergent roles in maintaining smoking behavior in men and women. While animal models of tobacco addiction that utilize nicotine self-administration have become more widely established, systematic examination of the multiple factors that instigate relapse to nicotine-seeking have been limited. Here, we examined nicotine self-administration and subsequent nicotine-seeking in male and female Sprague-Dawley rats using an animal model of self-administration and relapse. Rats lever pressed for nicotine (0.03 and 0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of lever responding. Once responding was extinguished, we examined the ability of previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations of drug+cues to reinstate nicotine-seeking. Both males and females readily acquired nicotine self-administration and displayed comparable levels of responding and intake at both nicotine doses. Following extinction, exposure to the previously nicotine-paired cues or yohimbine, but not the nicotine-prime alone, reinstated nicotine-seeking in males and females. Moreover, when combined with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No significant sex differences or estrous cycle dependent changes were noted across reinstatement tests. These results demonstrate the ability to reinstate nicotine-seeking with multiple modalities and that exposure to nicotine-associated cues during periods of a stressful state or nicotine can increase nicotine-seeking. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Smoking to Regulate Negative Affect: Disentangling the Relationship Between Posttraumatic Stress and Emotional Disorder Symptoms, Nicotine Dependence, and Cessation-Related Problems.

    Science.gov (United States)

    Mahaffey, Brittain L; Gonzalez, Adam; Farris, Samantha G; Zvolensky, Michael J; Bromet, Evelyn J; Luft, Benjamin J; Kotov, Roman

    2016-06-01

    Posttraumatic stress disorder (PTSD) is associated with various aspects of cigarette smoking, including higher levels of nicotine dependence and cessation difficulties. Affect-regulatory smoking motives are thought to, in part, underlie the association between emotional disorders such as PTSD and smoking maintenance, although few studies have empirically tested this possibility. Data were analyzed from 135 treatment-seeking smokers who were directly exposed to the World Trade Center disaster on September 11, 2001. We modeled the direct effect of 9/11 PTSD symptom severity on nicotine dependence, perceived barriers to smoking cessation, and severity of problematic symptoms experienced during prior cessation attempts. We also examined the indirect effect of PTSD on these outcomes via negative affect reduction smoking motives. Parallel models were constructed for additional emotional disorder symptoms, including panic and depressive symptoms. PTSD symptom severity was associated with nicotine dependence and perceived barriers to cessation, but not problems during prior quit attempts indirectly via negative affect reduction smoking motives. Panic and depressive symptoms both had significant indirect effects, via negative affect reduction smoking motives, on all three criterion variables. Affect-regulatory smoking motives appear to underlie associations between the symptoms of emotional disorders such as PTSD, panic, and depression in terms of smoking dependence and certain cessation-related criterion variables. Overall, this investigation suggests negative affect reduction smoking motives help to explain the relationship of PTSD, depression, and panic symptoms to nicotine dependence, severity of problems experienced during prior quit attempts and perceived barriers to cessation. These results highlight the importance of assessing motivations for smoking in the context of cessation treatment, especially among those with emotional disorder symptoms. Future interventions

  16. Concurrent nicotine and tobacco product use among homeless smokers and associations with cigarette dependence and other factors related to quitting.

    Science.gov (United States)

    Neisler, Julie; Reitzel, Lorraine R; Garey, Lorra; Kenzdor, Darla E; Hébert, Emily T; Vijayaraghavan, Maya; Businelle, Michael S

    2018-02-07

    Cigarette smoking rates among homeless adults are exceptionally high, contributing to health disparities experienced by this disadvantaged population. Concurrent nicotine and tobacco product use have been shown to result in greater health problems than cigarette smoking alone, and little is known about the rates, motives, and perceived impacts of concurrent use in this group. The purpose of this study is to explore concurrent use rates and constructs of interest among homeless adult daily smokers and to examine differences between concurrent users and non-concurrent users on cigarette dependence, perceived risk of smoking, readiness to quit, and the receipt of recent cessation intervention. Participants (N = 396) were recruited from six homeless-serving agencies and/or shelters in Oklahoma City. Enrolled participants completed self-report questionnaires. The rate of concurrent use was high -67.2%. Participants most frequently endorsed lower cost and a desire to cut down on cigarette smoking as motives for concurrent product use. Concurrent users indicated both a greater likelihood of developing a smoking-related disease if they did not quit for good and a greater number of past year quit attempts relative to non-concurrent users. There was no significant difference between concurrent users and non-concurrent users on readiness to quit or having received recent smoking cessation intervention. The need for cessation efforts that account for concurrent use for homeless adult smokers is great. Study findings indicate that concurrent users are commonly pursuing the reduction or elimination of cigarette usage and should be specifically targeted for cessation intervention. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  18. Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

    NARCIS (Netherlands)

    de Kloet, S.F.; Mansvelder, H.D.; de Vries, T.J.

    2015-01-01

    Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are

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

    Science.gov (United States)

    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.

  20. Electronic cigarettes and nicotine clinical pharmacology

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2004-11-01

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

  2. Impact of group motivational interviewing on enhancing treatment engagement for homeless Veterans with nicotine dependence and other substance use disorders: A pilot investigation.

    Science.gov (United States)

    Santa Ana, Elizabeth J; LaRowe, Steven D; Armeson, Kent; Lamb, Kayla E; Hartwell, Karen

    2016-10-01

    Prior studies have shown that Group Motivational Interviewing (GMI) for dually diagnosed patients holds promise for increasing treatment engagement. The current study evaluated the impact of a novel GMI protocol that included tobacco-specific components (referred to as "Tobacco GMI or T-GMI") targeting enhanced engagement in smoking cessation treatment. Thirty-seven primary alcohol and nicotine-dependent cigarette smoking homeless Veterans with co-morbid psychiatric conditions were recruited to receive four GMI sessions over 4 consecutive days. The first 16 participants received standard GMI, aimed at enhancing engagement in substance abuse treatment and for reducing substance use, while the remaining 21 participants received a modified "tobacco-specific" GMI protocol (T-GMI) that included additional content specific to cessation of tobacco use and enhancing smoking cessation treatment, in addition to the standard substance abuse content of GMI. Participants in T-GMI were more likely to attend tobacco cessation programming (p = .05), as well as to attend combined tobacco cessation programming with prescribed nicotine replacement therapy (p = .03), compared to those in standard GMI. Differences between treatment conditions with respect to alcohol and illicit drug use outcomes were not significant, although overall substance use declined over time in both groups. Results suggest that inclusion of tobacco-specific components in the context of GMI for substance abuse may enhance treatment engagement for tobacco cessation behaviors among dually diagnosed nicotine dependent homeless patients, a highly vulnerable population for which interventional resources targeting engagement in smoking cessation treatment has historically been lacking. (Am J Addict 2016;25:533-541). © 2016 American Academy of Addiction Psychiatry.

  3. Higher nicotine levels in schizophrenia compared with controls after smoking a single cigarette.

    Science.gov (United States)

    Williams, Jill M; Gandhi, Kunal K; Lu, Shou-En; Kumar, Supriya; Shen, Junwu; Foulds, Jonathan; Kipen, Howard; Benowitz, Neal L

    2010-08-01

    The increase in blood nicotine after smoking a single cigarette is nicotine boost. We hypothesized that smokers with schizophrenia (SCZ) have a greater nicotine boost than controls without this disorder. Twenty-one subjects (11 SCZ and 10 controls, CON) had repeated venous blood sampling before, during, and after smoking a single cigarette after 12-hr abstinence to measure nicotine concentrations. Blood samples were drawn at baseline (before smoking) and 1, 2, 4, 6, 8, 10, 20, 30, 60, 90, and 120 min after the first puff. Groups were similar in baseline characteristics, including gender and level of dependence, and all smoked 20-30 cigarettes/day. Area under the serum nicotine concentration-time curve (AUC(20)) was calculated for time up to 20 min after the start of smoking. The mean difference in AUC(20) was significantly greater for SCZ versus CON (135.4 ng-min/ml; 95% CI = 0.45-283.80). The shape of the nicotine concentration-time curve for SCZ was significantly different compared with controls (p smoking was higher in SCZ versus CON (25.2 vs. 11.1 ng/ml, p smoking. This technique improves on methods, which draw only two blood specimens to assess nicotine intake. Understanding how nicotine boost differs in SCZ from CON may explain high levels of addiction and low success in cessation in smokers with SCZ.

  4. Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats.

    Science.gov (United States)

    Vlachou, Styliani; Guery, Sebastien; Froestl, Wolfgang; Banerjee, Deboshri; Benedict, Jessica; Finn, M G; Markou, Athina

    2011-05-01

    γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA(B) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA(B) receptor agonists, GABA(B) receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. We examined whether the acute effects of the GABA(B) receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self-administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. These results showed that BHF177 selectively blocked nicotine self-administration and prevented cue-induced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA(B) receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans.

  5. Nicotine-induced embryonic malformations mediated by apoptosis from increasing intracellular calcium and oxidative stress.

    Science.gov (United States)

    Zhao, Zhiyong; Reece, E Albert

    2005-10-01

    Tobacco smoking by women during pregnancy increases the risk of congenital birth defects in the infants. Among the smoke products, nicotine is believed to be the major teratogenic factor that perturbs embryonic development. However, the role of nicotine in embryonic malformations has not been addressed, and the mechanisms by which nicotine affects embryonic development remain to be delineated. To investigate the effects of nicotine on early embryogenesis, murine embryos at embryonic day (E) 8.5 were dissected out of the uteri, cultured in a roller bottle system, and treated with nicotine (0.6-6 microM) or vehicle. Embryonic morphogenesis and growth were examined in terms of structural morphology and crown/rump length, respectively. Programmed cell death (apoptosis) was assessed using LysoTracker Red staining of whole mount embryos and TUNEL assay of tissue sections. Changes in intracellular calcium concentration ([Ca2+]i) and reactive oxygen species (ROS) production were assessed using fluorescent dyes (Flu-4, AM; H2DCFDA, respectively) under a confocal microscope. To further investigate the role of intracellular calcium and ROS in nicotine-induced embryopathy, embryos were treated with BAPTA-AM (2 microM) to inhibit [Ca2+]i elevation and ascorbic acid (vitamin C; 100 microg/ml) to scavenge ROS in presence of nicotine (6 microM). The embryos treated with nicotine in 3-6 microM were smaller than those treated with vehicle. Most of the embryos had open neural tube in the anterior (brain) regions. The embryos treated with 6 microM nicotine also exhibited severe defects in the posterior trunk, resembling caudal dysplasia. Excessive apoptosis was observed in the deformed structures. Significant increases in [Ca2+]i and ROS were seen in the tissues that had higher levels of apoptosis. Furthermore, inhibition of [Ca2+]i and scavenging of ROS significantly reduced embryonic malformation and apoptotic rates in the embryos. Nicotine affects embryonic development in a

  6. Effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Negus, S Stevens; Poklis, Justin L; Banks, Matthew L

    2015-10-01

    One complicating factor in cocaine addiction may be concurrent exposure and potential dependence on nicotine. The aim of the present study was to determine the effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in rhesus monkeys (Macaca mulatta). For comparison, we also determined effects of the nicotinic receptor antagonist mecamylamine on cocaine versus food choice during continuous saline and nicotine treatment. Rhesus monkeys (N = 3) responded under a concurrent schedule of food pellet (1 g) and intravenous cocaine (0-0.1 mg/kg/injection) availability. Saline and ascending nicotine doses (0.1-1.0 mg/kg/hr, intravenous) were continuously infused for 7-day treatment periods and separated by 24-hr saline treatment periods. Acute effects of mecamylamine (0.32-1.8 mg/kg, intramuscular, 15 min pretreatment) were determined during continuous saline and 0.32-mg/kg/hr nicotine treatments. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice. Nicotine treatment did not alter cocaine versus food choice. In contrast, preference of 0.032 mg/kg/injection cocaine was attenuated 24 hr following termination of 0.32-mg/kg/hr nicotine treatment, despite no somatic abstinence signs being observed. Acute mecamylamine enhanced cocaine choice during saline treatment and mainly suppressed rates of behavior during nicotine treatment. Overall, continuous nicotine exposure, up to 1 mg/kg/hr, does not enhance cocaine choice and does not produce nicotine dependence, as demonstrated by the lack of abstinence signs. (c) 2015 APA, all rights reserved).

  7. Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats

    OpenAIRE

    Semenova, Svetlana; Stolerman, Ian P.; Markou, Athina

    2007-01-01

    Nicotine appears to enhance attention, while nicotine withdrawal leads to attentional deficits in humans that are ameliorated with nicotine administration. However, there has been much debate as to whether nicotine improves performance under baseline conditions, or only ameliorates attentional deficits. Thus, we studied the effects of acute and chronic nicotine administration and nicotine withdrawal on attentional performance in the 5-choice serial reaction time task (5-CSRTT) in Wistar and S...

  8. Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement.

    Science.gov (United States)

    Fletcher, Paul J; Rizos, Zoë; Noble, Kevin; Soko, Ashlie D; Silenieks, Leo B; Lê, Anh Dzung; Higgins, Guy A

    2012-06-01

    The reinforcing effects of nicotine are mediated in part by brain dopamine systems. Serotonin, acting via 5-HT(2A) and 5-HT(2C) receptors, modulates dopamine function. In these experiments we examined the effects of the 5-HT(2C) receptor agonist Ro60-0175 and the 5-HT(2A) receptor antagonist (M100907, volinanserin) on nicotine self-administration and reinstatement of nicotine-seeking. Male Long-Evans rats self-administered nicotine (0.03 mg/kg/infusion, IV) on either a FR5 or a progressive ratio schedule of reinforcement. Ro60-0175 reduced responding for nicotine on both schedules. While Ro60-0175 also reduced responding for food reinforcement, response rates under drug treatment were several-fold higher than in animals responding for nicotine. M100907 did not alter responding for nicotine, or food, on either schedule. In tests of reinstatement of nicotine-seeking, rats were first trained to lever press for IV infusions of nicotine; each infusion was also accompanied by a compound cue consisting of a light and tone. This response was then extinguished over multiple sessions. Injecting rats with a nicotine prime (0.15 mg/kg) reinstated responding; reinstatement was also observed when responses were accompanied by the nicotine associated cue. Ro60-0175 attenuated reinstatement of responding induced by nicotine and by the cue. The effects of Ro60-0175 on both forms of reinstatement were blocked by the 5-HT(2C) receptor antagonist SB242084. M100907 also reduced reinstatement induced by either the nicotine prime or by the nicotine associated cue. The results indicate that 5-HT(2C) and 5-HT(2A) receptors may be potential targets for therapies to treat some aspects of nicotine dependence. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Nicotine Nasal Spray

    Science.gov (United States)

    Nicotine nasal spray is used to help people stop smoking. Nicotine nasal spray should be used together with a ... support groups, counseling, or specific behavior change techniques. Nicotine nasal spray is in a class of medications ...

  10. Nicotine replacement therapy

    Science.gov (United States)

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

  11. Nicotine Oral Inhalation

    Science.gov (United States)

    Nicotine oral inhalation is used to help people stop smoking. Nicotine oral inhalation should be used together with a ... support groups, counseling, or specific behavioral change techniques. Nicotine inhalation is in a class of medications called ...

  12. Validation of the human odor span task: effects of nicotine.

    Science.gov (United States)

    MacQueen, David A; Drobes, David J

    2017-10-01

    Amongst non-smokers, nicotine generally enhances performance on tasks of attention, with limited effect on working memory. In contrast, nicotine has been shown to produce robust enhancements of working memory in non-humans. To address this gap, the present study investigated the effects of nicotine on the performance of non-smokers on a cognitive battery which included a working memory task reverse-translated from use with rodents (the odor span task, OST). Nicotine has been reported to enhance OST performance in rats and the present study assessed whether this effect generalizes to human performance. Thirty non-smokers were tested on three occasions after consuming either placebo, 2 mg, or 4 mg nicotine gum. On each occasion, participants completed a battery of clinical and experimental tasks of working memory and attention. Nicotine was associated with dose-dependent enhancements in sustained attention, as evidenced by increased hit accuracy on the rapid visual information processing (RVIP) task. However, nicotine failed to produce main effects on OST performance or on alternative measures of working memory (digit span, spatial span, letter-number sequencing, 2-back) or attention (digits forward, 0-back). Interestingly, enhancement of RVIP performance occurred concomitant to significant reductions in self-reported attention/concentration. Human OST performance was significantly related to N-back performance, and as in rodents, OST accuracy declined with increasing memory load. Given the similarity of human and rodent OST performance under baseline conditions and the strong association between OST and visual 0-back accuracy, the OST may be particular useful in the study of conditions characterized by inattention.

  13. Treating nicotine dependence by targeting attention-deficit/ hyperactivity disorder (ADHD) with OROS methylphenidate: the role of baseline ADHD severity and treatment response.

    Science.gov (United States)

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

    2013-10-01

    To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) 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 ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions. Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ≥ 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (≤ 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). OROS methylphenidate, 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 medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD

  14. In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application.

    Science.gov (United States)

    Shin, Soo Hyeon; Thomas, Sherin; Raney, Sam G; Ghosh, Priyanka; Hammell, Dana C; El-Kamary, Samer S; Chen, Wilbur H; Billington, M Melissa; Hassan, Hazem E; Stinchcomb, Audra L

    2018-01-28

    The in vitro permeation test (IVPT) has been widely used to characterize the bioavailability (BA) of compounds applied on the skin. In this study, we performed IVPT studies using excised human skin (in vitro) and harmonized in vivo human serum pharmacokinetic (PK) studies to evaluate the potential in vitro-in vivo correlation (IVIVC) of nicotine BA from two, matrix-type, nicotine transdermal delivery systems (TDS). The study designs used for both in vitro and in vivo studies included 1h of transient heat (42±2°C) application during early or late time periods post-dosing. The goal was to evaluate whether any IVIVC observed would be evident even under conditions of heat exposure, in order to investigate further whether IVPT may have the potential to serve as a possible surrogate method to evaluate the in vivo effects of heat on the bioavailability of a drug delivered from a TDS. The study results have demonstrated that the BA of nicotine characterized by the IVPT studies correlated with and was predictive of the in vivo BA of nicotine from the respective TDS, evaluated under the matched study designs and conditions. The comparisons of single parameters such as steady-state concentration, heat-induced increase in partial AUCs and post-treatment residual content of nicotine in TDS from the in vitro and in vivo data sets showed no significant differences (p≥0.05). In addition, a good point-to-point IVIVC (Level A correlation) for the entire study duration was achieved by predicting in vivo concentrations of nicotine using two approaches: Approach I requiring only an in vitro data set and Approach II involving deconvolution and convolution steps. The results of our work suggest that a well designed IVPT study with adequate controls can be a useful tool to evaluate the relative effects of heat on the BA of nicotine from TDS with different formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent

    Directory of Open Access Journals (Sweden)

    Puliyappadamba Vineshkumar T

    2010-08-01

    Full Text Available Abstract Background Lung cancer is the most lethal cancer and almost 90% of lung cancer is due to cigarette smoking. Even though nicotine, one of the major ingredients of cigarette smoke and the causative agent for addiction, is not a carcinogen by itself, several investigators have shown that nicotine can induce cell proliferation and angiogenesis. We observed that the proliferative index of nicotine is different in the lung cancer cell lines H1299 (p53-/- and A549 (p53+/+ which indicates that the mode of up-regulation of survival signals by nicotine might be different in cells with and without p53. Results While low concentrations of nicotine induced activation of NF-κB, Akt, Bcl2, MAPKs, AP1 and IAPs in H1299, it failed to induce NF-κB in A549, and compared to H1299, almost 100 times higher concentration of nicotine was required to induce all other survival signals in A549. Transfection of WT-p53 and DN-p53 in H1299 and A549 respectively, reversed the mode of activation of survival signals. Curcumin down-regulated all the survival signals induced by nicotine in both the cells, irrespective of their p53 status. The hypothesis was confirmed when lower concentrations of nicotine induced NF-κB in two more lung cancer cells, Hop-92 and NCI-H522 with mutant p53 status. Silencing of p53 in A549 using siRNA made the cells susceptible to nicotine-induced NF-κB nuclear translocation as in A549 DN-p53 cells. Conclusions The present study reveals a detrimental role of nicotine especially in lung cancer patients with impaired p53 status and identifies curcumin as a potential chemopreventive.

  16. Testing environment shape differentially modulates baseline and nicotine-induced changes in behavior: Sex differences, hypoactivity, and behavioral sensitization.

    Science.gov (United States)

    Illenberger, J M; Mactutus, C F; Booze, R M; Harrod, S B

    2018-02-01

    In those who use nicotine, the likelihood of dependence, negative health consequences, and failed treatment outcomes differ as a function of gender. Women may be more sensitive to learning processes driven by repeated nicotine exposure that influence conditioned approach and craving. Sex differences in nicotine's influence over overt behaviors (i.e. hypoactivity or behavioral sensitization) can be examined using passive drug administration models in male and female rats. Following repeated intravenous (IV) nicotine injections, behavioral sensitization is enhanced in female rats compared to males. Nonetheless, characteristics of the testing environment also mediate rodent behavior following drug administration. The current experiment used a within-subjects design to determine if nicotine-induced changes in horizontal activity, center entries, and rearing displayed by male and female rats is detected when behavior was recorded in round vs. square chambers. Behaviors were recorded from each group (males-round: n=19; males-square: n=18; females-square: n=19; and females-round: n=19) immediately following IV injection of saline, acute nicotine, and repeated nicotine (0.05mg/kg/injection). Prior to nicotine treatment, sex differences were apparent only in round chambers. Following nicotine administration, the order of magnitude for the chamber that provided enhanced detection of hypoactivity or sensitization was contingent upon both the dependent measure under examination and the animal's biological sex. As such, round and square testing chambers provide different, and sometimes contradictory, accounts of how male and female rats respond to nicotine treatment. It is possible that a central mechanism such as stress or cue sensitivity is impacted by both drug exposure and environment to drive the sex differences observed in the current experiment. Until these complex relations are better understood, experiments considering sex differences in drug responses should balance

  17. Genetic factors control nicotine self-administration in isogenic adolescent rat strains.

    Directory of Open Access Journals (Sweden)

    Hao Chen

    Full Text Available Adult cigarette smokers usually become dependent on cigarettes during adolescence. Despite recent advances in addiction genetics, little data delineates the genetic factors that account for the vulnerability of humans to smoke tobacco. We studied the operant nicotine self-administration (SA behavior of six inbred strains of adolescent male rats (Fisher 344, Brown Norway, Dark Agouti, Spontaneous Hypertensive Rat, Wistar Kyoto and Lewis and six selected F1 hybrids. All rats were trained to press a lever to obtain food starting on postnatal day (PN 32, and then nicotine (0.03 mg/kg/infusion, i.v. reinforcement was made available on PN41-42 (10 consecutive daily 2 h sessions. Of the 12 isogenic strains, Fisher rats self-administered the fewest nicotine infusions (1.45 ± 0.36/d during the last 3 d, while Lewis rats took the most nicotine (13.0 ± 1.4/d. These strains sorted into high, intermediate and low self-administration groups in 2, 2, and 8 strains, respectively. The influence of heredity on nicotine SA (0.64 is similar to that reported for humans. Therefore, this panel of isogenic rat strains effectively models the overall impact of genetics on the vulnerability to acquire nicotine-reinforced behavior during adolescence. Separate groups of rats responded for food starting on PN41. The correlation between nicotine and food reward was not significant. Hence, the genetic control of the motivation to obtain nicotine is distinctly different from food reward, indicating the specificity of the underlying genetic mechanisms. Lastly, the behavior of F1 hybrids was not predicted from the additive behavior of the parental strains, indicating the impact of significant gene-gene interactions on the susceptibility to nicotine reward. Taken together, the behavioral characteristics of this model indicate its strong potential to identify specific genes mediating the human vulnerability to smoke cigarettes.

  18. Association and interaction analyses of 5-HT3 receptor and serotonin transporter genes with alcohol, cocaine, and nicotine dependence using the SAGE data.

    Science.gov (United States)

    Yang, Jiekun; Li, Ming D

    2014-07-01

    Previous studies have implicated genes encoding the 5-HT3AB receptors (HTR3A and HTR3B) and the serotonin transporter (SLC6A4), both independently and interactively, in alcohol (AD), cocaine (CD), and nicotine dependence (ND). However, whether these genetic effects also exist in subjects with comorbidities remains largely unknown. We used 1,136 African-American (AA) and 2,428 European-American (EA) subjects from the Study of Addiction: Genetics and Environment (SAGE) to determine associations between 88 genotyped or imputed variants within HTR3A, HTR3B, and SLC6A4 and three types of addictions, which were measured by DSM-IV diagnoses of AD, CD, and ND and the Fagerström Test for Nicotine Dependence (FTND), an independent measure of ND commonly used in tobacco research. Individual SNP-based association analysis revealed a significant association of rs2066713 in SLC6A4 with FTND in AA (β = -1.39; P = 1.6E - 04). Haplotype-based association analysis found one major haplotype formed by SNPs rs3891484 and rs3758987 in HTR3B that was significantly associated with AD in the AA sample, and another major haplotype T-T-G, formed by SNPs rs7118530, rs12221649, and rs2085421 in HTR3A, which showed significant association with FTND in the EA sample. Considering the biologic roles of the three genes and their functional relations, we used the GPU-based Generalized Multifactor Dimensionality Reduction (GMDR-GPU) program to test SNP-by-SNP interactions within the three genes and discovered two- to five-variant models that have significant impacts on AD, CD, ND, or FTND. Interestingly, most of the SNPs included in the genetic interaction model(s) for each addictive phenotype are either overlapped or in high linkage disequilibrium for both AA and EA samples, suggesting these detected variants in HTR3A, HTR3B, and SLC6A4 are interactively contributing to etiology of the three addictive phenotypes examined in this study.

  19. Renal transport and metabolism of nicotinic acid

    International Nuclear Information System (INIS)

    Schuette, S.; Rose, R.C.

    1986-01-01

    Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

  20. Passive immunization against nicotine attenuates nicotine discrimination.

    Science.gov (United States)

    Malin, David H; Alvarado, Candice L; Woodhouse, Katherine S; Karp, Hilary; Urdiales, Evelyn; Lay, Diana; Appleby, Phillip; Moon, William D; Ennifar, Sofiane; Basham, Lisa; Fattom, Ali

    2002-04-26

    Ten rats were trained in a two lever operant chamber to press different levers after a nicotine injection (0.14 mg/kg s.c.) or a saline injection on an FR10 schedule. The rats were then injected i.p. with either 150 mg nicotine-specific IgG or the same amount of control IgG from non-immunized rabbits. On successive days, they were retested with both levers active after a saline injection, a full training dose of nicotine and a half dose of nicotine (0.07 mg/kg s.c.). After saline injection, both groups pressed the saline lever almost exclusively. After each of the nicotine doses, the immunized rats performed a significantly lower percentage of their lever presses on the nicotine lever than did non-immunized rats. The results suggest that passive immunization can interfere with the stimulus properties of nicotine.

  1. Nicotine induces cell proliferation in association with cyclin D1 up-regulation and inhibits cell differentiation in association with p53 regulation in a murine pre-osteoblastic cell line

    International Nuclear Information System (INIS)

    Sato, Tsuyoshi; Abe, Takahiro; Nakamoto, Norimichi; Tomaru, Yasuhisa; Koshikiya, Noboru; Nojima, Junya; Kokabu, Shoichiro; Sakata, Yasuaki; Kobayashi, Akio; Yoda, Tetsuya

    2008-01-01

    Recent studies have suggested that nicotine critically affects bone metabolism. Many studies have examined the effects of nicotine on proliferation and differentiation, but the underlying molecular mechanisms remain unclear. We examined cell cycle regulators involved in the proliferation and differentiation of MC3T3-E1 cells. Nicotine induced cell proliferation in association with p53 down-regulation and cyclin D1 up-regulation. In differentiated cells, nicotine reduced alkaline phosphatase activity and mineralized nodule formation in dose-dependent manners. Furthermore, p53 expression was sustained in nicotine-treated cells during differentiation. These findings indicate that nicotine promotes the cell cycle and inhibits differentiation in association with p53 regulation in pre-osteoblastic cells

  2. Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking

    Directory of Open Access Journals (Sweden)

    Ami eCohen

    2013-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. Affinities of bispyridinium non-oxime compounds to [(3)H]epibatidine binding sites of Torpedo californica nicotinic acetylcholine receptors depend on linker length.

    Science.gov (United States)

    Niessen, K V; Seeger, T; Tattersall, J E H; Timperley, C M; Bird, M; Green, C; Thiermann, H; Worek, F

    2013-12-05

    The toxicity of organophosphorus nerve agents or pesticides arises from accumulation of acetylcholine and overstimulation of both muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) due to inhibition of acetylcholinesterase (AChE). Standard treatment by administration of atropine and oximes, e.g., obidoxime or pralidoxime, focuses on antagonism of mAChRs and reactivation of AChE, whereas nicotinic malfunction is not directly treated. An alternative approach would be to use nAChR active substances to counteract the effects of accumulated acetylcholine. Promising in vitro and in vivo results were obtained with the bispyridinium compounds SAD-128 (1,1'-oxydimethylene bis(4-tert-butylpyridinium) dichloride) and MB327 (1,1'-(propane-1,3-diyl)bis(4-tert-butylpyridinium) di(iodide)), which were partly attributed to their interaction with nAChRs. In this study, a homologous series of unsubstituted and 4-tert-butyl-substituted bispyridinium compounds with different alkane linker lengths was investigated in competition binding experiments using [(3)H]epibatidine as a reporter ligand. Additionally, the effect of the well-characterised MB327 on the [(3)H]epibatidine equilibrium dissociation (KD) constant in different buffers was determined. This study demonstrated that divalent cations increased the affinity of [(3)H]epibatidine. Since quaternary ammonium molecules are known to inhibit AChE, the obtained affinity constants of the tested bispyridinium compounds were compared with the inhibition of human AChE. In competition experiments, bispyridinium derivatives of longer linker length displaced [(3)H]epibatidine and inhibited AChE strongly. Bispyridinium compounds with short linkers, at most, have an allosteric interaction with the [(3)H]epibatidine binding sites and barely inhibited AChE. In dependence on alkane linker length, the bispyridinium compounds seemed to interact at different binding sites. However, the exact binding sites of the bispyridinium

  5. α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way

    Directory of Open Access Journals (Sweden)

    Andrea Grandi

    2017-11-01

    Full Text Available The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α7 nAChRs stimulation is still controversial and the potential contribution of α4β2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α7 and α4β2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403 and antagonists (methyllycaconitine and dihydro-β-erythroidine of α7 and α4β2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α4β2 ligands evoked weak and contradictory effects, while α7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

  6. Self-reported smoking effects and comparative value between cigarettes and high dose e-cigarettes in nicotine-dependent cigarette smokers.

    Science.gov (United States)

    McPherson, Sterling; Howell, Donelle; Lewis, Jennifer; Barbosa-Leiker, Celestina; Bertotti Metoyer, Patrick; Roll, John

    2016-04-01

    The objective of this experiment was to evaluate the comparative value of cigarettes versus high dose e-cigarettes among nicotine-dependent cigarette smokers when compared with money or use of their usual cigarette brand. The experiment used a within-subject design with four sessions. After baseline assessment, participants attended two 15-min unrestricted smoking sessions: one cigarette smoking session and one e-cigarette smoking session. Participants then attended two multiple-choice procedure (MCP) sessions: a session comparing cigarettes and money and a session comparing e-cigarettes and money. Participants (n=27) had used cigarettes regularly, had never used e-cigarettes, and were not currently attempting to quit smoking. The sample consisted primarily of males (72%), with a mean age of 34 years. When given the opportunity to choose between smoking a cigarette or an e-cigarette, participants chose the cigarette 73.9% of the time. Findings from the MCP demonstrated that after the first e-cigarette exposure sessions, the crossover value for cigarettes ($3.45) was significantly higher compared with the crossover value for e-cigarettes ($2.73). The higher participant preference, self-reported smoking effects, and higher MCP crossover points indicate that cigarettes have a higher comparative value than high dose e-cigarettes among e-cigarette naive smokers.

  7. Difference in the functional connectivity of the dorsolateral prefrontal cortex between smokers with nicotine dependence and individuals with internet gaming disorder.

    Science.gov (United States)

    Ge, Xin; Sun, Yawen; Han, Xu; Wang, Yao; Ding, Weina; Cao, Mengqiu; Du, Yasong; Xu, Jianrong; Zhou, Yan

    2017-07-27

    It has been reported that internet gaming disorder (IGD) and smokers with nicotine dependence (SND) share clinical characteristics, such as over-engagement despite negative consequences and cravings. This study is to investigate the alterations in the resting-state functional connectivity (rsFC) of the dorsolateral prefrontal cortex (DLPFC) observed in SND and IGD. In this study, 27 IGD, 29 SND, and 33 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. DLPFC connectivity was determined in all participates by investigating the synchronized low-frequency fMRI signal fluctuations using a temporal seed-based correlation method. Compared with the HC group, the IGD and SND groups showed decreased rsFC with DLPFC in the right insula and left inferior frontal gyrus with DLPFC. Compared with SND group, the IGD subjects exhibited increased rsFC in the left inferior temporal gyrus and right inferior orbital frontal gyrus and decreased rsFC in the right middle occipital gyrus, supramarginal gyrus, and cuneus with DLPFC. Our results confirmed that SND and IGD share similar neural mechanisms related to craving and impulsive inhibitions. The significant difference in rsFC with DLPFC between the IGD and SND subjects may be attributed to the visual and auditory stimulation generated by long-term internet gaming.

  8. Decaffeinated Coffee and Nicotine-Free Tobacco Provide Neuroprotection in Drosophila Models of Parkinson's Disease through an NRF2-Dependent Mechanism

    OpenAIRE

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

    2010-01-01

    Epidemiological studies have revealed a significantly reduced risk of Parkinson's disease (PD) among coffee and tobacco users, although it is unclear whether these correlations reflect neuroprotective/symptomatic effects of these agents or preexisting differences in the brains of tobacco and coffee users. Here, we report that coffee and tobacco, but not caffeine or nicotine, are neuroprotective in fly PD models. We further report that decaffeinated coffee and nicotine-free tobacco are as neur...

  9. A flexible model for actuarial risks under dependence

    NARCIS (Netherlands)

    Albers, Willem/Wim; Kallenberg, W.C.M.; Lukocius, V.

    Methods for computing risk measures, such as stop-loss premiums, tacitly assume independence of the underlying individual risks. This can lead to huge errors even when only small dependencies occur. In the present paper, a general model is developed which covers what happens in practice in a

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

    Science.gov (United States)

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

    2015-07-11

    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. 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. 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. 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 novel object recognition deficits are

  11. Behavioral effects of nicotine exposure from secondhand tobacco smoke among bar and restaurant workers.

    Science.gov (United States)

    Okoli, Chizimuzo T C; Rayens, Mary Kay; Hahn, Ellen J

    2007-09-01

    This study explores the behavioral effects of nicotine exposure from secondhand tobacco smoke (SHS) on bar and restaurant workers. Baseline data were obtained from a longitudinal study of 105 bar and restaurant workers. Hair nicotine, self-reported SHS exposure, smoking status, symptoms of nicotine exposure after being exposed to a smoky environment, and nicotine dependence were assessed. Nonsmokers reporting four or more symptoms of nicotine exposure had higher hair nicotine levels than those reporting less than four symptoms. Nonsmokers with higher hair nicotine levels were 2.2 times more likely to report 4 or more behavioral symptoms. Self-reported secondhand tobacco smoke exposure and hair nicotine were not predictive of nicotine dependence among smokers. Nicotine exposure from secondhand tobacco smoke may have important behavioral outcomes in nonsmokers. This study provides further evidence for the importance of prohibiting smoking in hospitality venues to protect the health of workers.

  12. The estrogen-dependent baroreflex dysfunction caused by nicotine in female rats is mediated via NOS/HO inhibition: Role of sGC/PI3K/MAPKERK

    International Nuclear Information System (INIS)

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

    2015-01-01

    We have previously reported that estrogen (E2) exacerbates the depressant effect of chronic nicotine on arterial baroreceptor activity in female rats. Here, we tested the hypothesis that this nicotine effect is modulated by nitric oxide synthase (NOS) and/or heme oxygenase (HO) and their downstream soluble guanylate cyclase (sGC)/phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinases (MAPKs) signaling. We investigated the effects of (i) inhibition or facilitation of NOS or HO on the interaction of nicotine (2 mg/kg/day i.p., 2 weeks) with reflex bradycardic responses to phenylephrine in ovariectomized (OVX) rats treated with E2 or vehicle, and (ii) central pharmacologic inhibition of sGC, PI3K, or MAPKs on the interaction. The data showed that the attenuation by nicotine of reflex bradycardia in OVXE2 rats was abolished after treatment with hemin (HO inducer) or L-arginine (NOS substrate). The hemin or L-arginine effect disappeared after inhibition of NOS (Nω-Nitro-L-arginine methyl ester hydrochloride, L-NAME) and HO (zinc protoporphyrin IX, ZnPP), respectively, denoting the interaction between the two enzymatic pathways. E2-receptor blockade (ICI 182,780) reduced baroreflexes in OVXE2 rats but had no effect on baroreflex improvement induced by hemin or L-arginine. Moreover, baroreflex enhancement by hemin was eliminated following intracisternal (i.c.) administration of wortmannin, ODQ, or PD98059 (inhibitors of PI3K, sGC, and extracellular signal-regulated kinases, MAPK ERK , respectively). In contrast, the hemin effect was preserved after inhibition of MAPK p38 (SB203580) or MAPK JNK (SP600125). Overall, NOS/HO interruption underlies baroreflex dysfunction caused by nicotine in female rats and the facilitation of NOS/HO-coupled sGC/PI3K/MAPK ERK signaling might rectify the nicotine effect. - Highlights: • Hemin or L-arginine blunts baroreflex dysfunction caused by nicotine in OVXE2 rats. • NO/CO crosstalk mediates favorable baroreflex effect

  13. [A preliminary study on the autophagy level of human periodontal ligament cells regulated by nicotine].

    Science.gov (United States)

    Yang, Du; Shuai, Yuan; Zhifei, Zhou; Lizheng, Wu; Lulu, Wang; Xing'an, Wu; Xiaojing, Wang

    2017-04-01

    To explore the effect of nicotine on the autophagy level of human periodontal ligament cells (hPDLCs). Periodontal tissues collected from premolars for orthodontic treatment reasons were used to culture hPDLCs. Western blot analysis was performed to test the most optimal time and concentration of nicotine on the autophagy level of the hPDLCs. Transmission electron microscope and immunofluorescence observation were carried out to detect the form of autophagosomes and expression of autophagy related protein LC3 in hPDLCs under this optimal condition. Protein expression of LC3Ⅱ was up regulated with the 12 h nicotine stimulating. Besides that, the up regulation of the protein expression of LC3Ⅱ was concentration dependent and nicotine with a concentration of 1×10⁻⁵ mol·L⁻¹ was the most optimal condition. Transmission electron microscope and immunofluorescence observations indicated that nicotine would activate the autophagy level of hPDLCs by increasing the number of autophagosomes and up regulating the expression of autophagy related protein LC3. Nicotine could increase autophagy level of hPDLCs, thus affecting the occurrence and development of smoking related periodontitis.

  14. [Drugs used to treat nicotine addiction].

    Science.gov (United States)

    Zieleń, Iwona; Sliwińska-Mossoń, Mariola; Milnerowicz, Halina

    2012-01-01

    Tobacco smoking in Poland is fairly widespread on a large scale. Research suggests that the early twenty-first century, the percentage of female daily smokers aged 20 and above was 26%, and men the same age 43%. In addition, epidemiological studies have shown that smoking was the cause of approximately sixty-nine thousand deaths in Poland (including fifty-seven thousand men and twelve thousand women). It is common ground that cigarette smoking has a negative effect on our body. It represents one of the main and most commonly defined risk factors for many diseases that can be eliminated. Smoking often leads to addiction, and nicotine is an addictive drug. Nicotine addiction is characterized by symptoms such as: "hunger" smoking, difficulty in controlling behavior on smoking or the number of cigarettes smoked, nicotine withdrawal, the occurrence of tolerance, neglect of interests, as well as devoting more time on activities related to smoking, follow-up smoking despite knowledge of its dangers. The most commonly used in Poland, a questionnaire to identify nicotine dependence is a test Fagerstöma. Currently assigned some importance, "the doctor a conversation the patient" and motivating him to stop smoking and maintain abstinence as long as possible. But beyond the "conversation" is also used as an aid to medical treatment for the patient to stop smoking, especially to alleviate withdrawal symptoms. The first attempts of pharmacological help in the effort to weaning from smoking began in the thirties. Were conducted fairly successful, although uncontrolled trials with lobeline, an alkaloid of action similar to nicotine. In Poland, the drugs of first choice in the treatment of nicotine dependence are nicotine replacement therapies (nicotine gum and patches that contain nicotine) and bupropion SR. Quite a popular drugs to help in the fight against addiction are also cytisine and varenicline. The choice of the drug is usually the result of medical experience in the use

  15. Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates.

    Science.gov (United States)

    Jacobs, David S; Barkin, Claire E; Kohut, Michelle R; Bergman, Jack; Kohut, Stephen J

    2017-12-01

    Accumulating evidence suggests that the FDA-approved serotonin 5-HT 2C receptor agonist, lorcaserin (Belviq ® ), may be a promising candidate for the management of substance use disorders, including nicotine addiction. The present study was conducted to determine the efficacy and selectivity of acute or continuous lorcaserin treatment for decreasing the reinforcing effects of nicotine in a primate species. Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2years) responded for injections of nicotine (0.32-100μg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement during daily 100-min sessions. When responding was stable, lorcaserin was administered either as an acute pretreatment (0.1-1.0mg/kg, IM) or by continuous infusion (0.1mg/kg/hr, SC for 3-5days). Daily activity patterns were also monitored immediately following experimental sessions. Results indicate that acute lorcaserin pretreatment produced significant and dose-dependent decreases in nicotine-maintained responding across a >100-fold range of self-administered nicotine doses. Continuous lorcaserin treatment decreased intake of 10μg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding was only moderately decreased in 3 of 4 subjects after acute administration and unaffected in all subjects during continuous treatment. Daily activity also was significantly decreased-to ≤50% of control values-following experimental sessions in which acute lorcaserin was administered. These data indicate that lorcaserin reduces IV self-administration of nicotine at a dose that decreases motoric activity but less consistently disrupts food-maintained responding. Further research into lorcaserin's potential utility for the management of nicotine dependence is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Studies on the nicotine exposure of individual smokers. I. Changes in mouth-level exposure to nicotine on switching to lower nicotine cigarettes.

    Science.gov (United States)

    Forbes, W F; Robinson, J C; Hanley, J A; Colburn, H N

    1976-01-01

    Twenty-four subjects smoked two brands of filter-tipped cigarettes delivering different amounts of nicotine, on the following 4-week schedule: 1. Smoking their usual brand for 1 week. 2. Smoking another brand similar in size, but delivering less nicotine, for 2 weeks. 3. Reverting to their usual brand for 1 week. The amount of nicotine entering the mouth, defined as the mouth-level exposure, was estimated from a determination of the amount of nicotine trapped in the filter of each cigarette smoked. The results indicate a substantial variation in mouth-level exposure for the subjects studied, even among smokers of cigarettes that deliver similar amounts of nicotine when smoked on a machine under standard conditions. For the majority of subjects, however, changing to a lower nicotine cigarette reduced the total daily mouth-level exposure to nicotine and, therefore, presumably the total tar intake.

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

    Science.gov (United States)

    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.

  18. The metabolic fate of nectar nicotine in worker honey bees.

    Science.gov (United States)

    du Rand, Esther E; Pirk, Christian W W; Nicolson, Susan W; Apostolides, Zeno

    2017-04-01

    Honey bees (Apis mellifera) are generalist pollinators that forage for nectar and pollen of a very large variety of plant species, exposing them to a diverse range of secondary metabolites produced as chemical defences against herbivory. Honey bees can tolerate high levels of many of these toxic compounds, including the alkaloid nicotine, in their diet without incurring apparent fitness costs. Very little is known about the underlying detoxification processes mediating this tolerance. We examined the metabolic fate of nicotine in newly emerged worker bees using radiolabeled nicotine and LC-MS/MS analysis to determine the kinetic distribution profile of nicotine as well as the absence or presence and identity of any nicotine-derived metabolites. Nicotine metabolism was extensive; virtually no unmetabolised nicotine were recovered from the rectum. The major metabolite found was 4-hydroxy-4-(3-pyridyl) butanoic acid, the end product of 2'C-oxidation of nicotine. It is the first time that 4-hydroxy-4-(3-pyridyl) butanoic acid has been identified in an insect as a catabolite of nicotine. Lower levels of cotinine, cotinine N-oxide, 3'hydroxy-cotinine, nicotine N-oxide and norcotinine were also detected. Our results demonstrated that formation of 4-hydroxy-4-(3-pyridyl) butanoic acid is quantitatively the most significant pathway of nicotine metabolism in honey bees and that the rapid excretion of unmetabolised nicotine does not contribute significantly to nicotine tolerance in honey bees. In nicotine-tolerant insects that do not rely on the rapid excretion of nicotine like the Lepidoptera, it is possible that the 2'C-oxidation of nicotine is the conserved metabolic pathway instead of the generally assumed 5'C-oxidation pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Targeting nicotine addiction: the possibility of a therapeutic vaccine

    Directory of Open Access Journals (Sweden)

    Escobar-Chávez JJ

    2011-04-01

    Full Text Available José Juan Escobar-Chávez1, Clara Luisa Domínguez-Delgado2, Isabel Marlen Rodríguez-Cruz21Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, México; 2División de Estudios de Posgrado (Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, MéxicoAbstract: Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results

  20. Auditory target processing in methadone substituted opiate addicts: The effect of nicotine in controls

    Directory of Open Access Journals (Sweden)

    Zerbin Dieter

    2007-11-01

    Full Text Available Abstract Background The P300 component of the auditory evoked potential is an indicator of attention dependent target processing. Only a few studies have assessed cognitive function in substituted opiate addicts by means of evoked potential recordings. In addition, P300 data suggest that chronic nicotine use reduces P300 amplitudes. While nicotine and opiate effects combine in addicted subjects, here we investigated the P300 component of the auditory event related potential in methadone substituted opiate addicts with and without concomitant non-opioid drug use in comparison to a group of control subjects with and without nicotine consumption. Methods We assessed 47 opiate addicted out-patients under current methadone substitution and 65 control subjects matched for age and gender in an 2-stimulus auditory oddball paradigm. Patients were grouped for those with and without additional non-opioid drug use and controls were grouped for current nicotine use. P300 amplitude and latency data were analyzed at electrodes Fz, Cz and Pz. Results Patients and controls did not differ with regard to P300 amplitudes and latencies when whole groups were compared. Subgroup analyses revealed significantly reduced P300 amplitudes in controls with nicotine use when compared to those without. P300 amplitudes of methadone substituted opiate addicts were in between the two control groups and did not differ with regard to additional non-opioid use. Controls with nicotine had lower P300 amplitudes when compared to patients with concomitant non-opioid drugs. No P300 latency effects were found. Conclusion Attention dependent target processing as indexed by the P300 component amplitudes and latencies is not reduced in methadone substituted opiate addicts when compared to controls. The effect of nicotine on P300 amplitudes in healthy subjects exceeds the effects of long term opioid addiction under methadone substitution.

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

    Science.gov (United States)

    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.

  2. Alcohol use disorders, nicotine dependence, and co-occurring mood and anxiety disorders in the United States and South Korea-a cross-national comparison.

    Science.gov (United States)

    Chou, S Patricia; Lee, Hae K; Cho, Maeng J; Park, Jong-Ik; Dawson, Deborah A; Grant, Bridget F

    2012-04-01

    The strong comorbidity between substance use disorders (SUDs) and mood and anxiety disorders has been well documented. In view of lack of research findings addressing the co-occurrence of SUDs and mood and anxiety disorders, this study examined the pattern of comorbidity of alcohol use disorders (AUDs) and nicotine dependence (ND) between 2 culturally diverse countries, the United States and South Korea. Using the nationally representative samples of the U.S. and Korean general populations, we directly compared rates and comorbidity patterns of AUDs, ND, and mood and anxiety disorders between the 2 countries. We further examined the rates and the comorbidity pattern among individuals with AUDs who sought treatment in the last 12 months. Twelve-month prevalence rates were derived to estimate country differentials, and odds ratios (ORs) and 95% confidence intervals were estimated to measure the strength of comorbid associations while adjusting for all sociodemographic characteristics in multivariate logistic models specific to each country. The 12-month prevalence rates of AUDs, ND, and any mood disorder and any anxiety disorder were 9.7, 14.4, 9.5, and 11.9% among Americans, whereas the corresponding rates were 7.1, 6.6, 2.0, and 5.2% among Koreans. These rates were significantly greater (except for any AUD) among Americans than among their Korean counterparts. With respect to comorbidity, both countries showed comparable patterns that the prevalence rates of mood and anxiety disorders were consistently the highest among persons with alcohol dependence (AD). Also, a disparate pattern was observed in Korea that the prevalence rates of mood and anxiety disorders were generally lower among individuals with ND than among those with alcohol abuse and AD. Furthermore, despite significantly greater prevalence of AD in Korea (5.1%) than in the United States (4.4%), alcohol-dependent Americans were 4 times (OR = 3.93) more likely to seek treatment compared to their Korean

  3. Pricing of path dependent derivatives with discretely monitored underlying assets

    Science.gov (United States)

    Choi, Hyomin

    This dissertation presents two different approaches to path dependent option pricing with discrete sampling. Provided the underlying asset of a path dependent derivative contract follows an affine process, we use the forward characteristic method to evaluate its fair price. Our study shows that the valuation method is numerically accessible as long as the contract payoff is a linear combination of log return of its underlying asset price. We compute various examples of such contracts and give contract-tailored formulas that we use in these examples. In the second part, we consider variance options under stochastic volatility model. We analyze the difference between variance option prices with discrete and continuous sampling as a function of N, the number of observations made in the former. We find the series expansion of the difference with respect to 1/N and find its leading term. By adding this leading term to the value of continuously sampled variance option, we obtain a simple and well-understood approximation of discretely sample variance option price.

  4. Size-dependent structure of silver nanoparticles under high pressure

    Energy Technology Data Exchange (ETDEWEB)

    Koski, Kristie Jo [Univ. of California, Berkeley, CA (United States)

    2008-12-31

    Silver noble metal nanoparticles that are<10 nm often possess multiply twinned grains allowing them to adopt shapes and atomic structures not observed in bulk materials. The properties exhibited by particles with multiply twinned polycrystalline structures are often far different from those of single-crystalline particles and from the bulk. I will present experimental evidence that silver nanoparticles<10 nm undergo a reversible structural transformation under hydrostatic pressures up to 10 GPa. Results for nanoparticles in the intermediate size range of 5 to 10 nm suggest a reversible linear pressure-dependent rhombohedral distortion which has not been previously observed in bulk silver. I propose a mechanism for this transitiion that considers the bond-length distribution in idealized multiply twinned icosahedral particles. Results for nanoparticles of 3.9 nm suggest a reversible linear pressure-dependent orthorhombic distortion. This distortion is interpreted in the context of idealized decahedral particles. In addition, given these size-dependent measurements of silver nanoparticle compression with pressure, we have constructed a pressure calibration curve. Encapsulating these silver nanoparticles in hollow metal oxide nanospheres then allows us to measure the pressure inside a nanoshell using x-ray diffraction. We demonstrate the measurement of pressure gradients across nanoshells and show that these nanoshells have maximum resolved shear strengths on the order of 500 MPa to IGPa.

  5. Mechanisms of Nicotinic Modulation of Glutamatergic Neuroplasticity in Humans.

    Science.gov (United States)

    Lugon, Marcelo Di Marcello Valladão; Batsikadze, Giorgi; Fresnoza, Shane; Grundey, Jessica; Kuo, Min-Fang; Paulus, Walter; Nakamura-Palacios, Ester Miyuki; Nitsche, Michael A

    2017-01-01

    The impact of nicotine (NIC) on plasticity is thought to be primarily determined via calcium channel properties of nicotinic receptor subtypes, and glutamatergic plasticity is likewise calcium-dependent. Therefore glutamatergic plasticity is likely modulated by the impact of nicotinic receptor-dependent neuronal calcium influx. We tested this hypothesis for transcranial direct current stimulation (tDCS)-induced long-term potentiation-like plasticity, which is abolished by NIC in nonsmokers. To reduce calcium influx under NIC, we blocked N-methyl-d-aspartate (NMDA) receptors. We applied anodal tDCS combined with 15 mg NIC patches and the NMDA-receptor antagonist dextromethorphan (DMO) in 3 different doses (50, 100, and 150 mg) or placebo medication. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor-evoked potential amplitudes after plasticity induction. NIC abolished anodal tDCS-induced motor cortex excitability enhancement, which was restituted under medium dosage of DMO. Low-dosage DMO did not affect the impact of NIC on tDCS-induced plasticity and high-dosage DMO abolished plasticity. For DMO alone, the low dosage had no effect, but medium and high dosages abolished tDCS-induced plasticity. These results enhance our knowledge about the proposed calcium-dependent impact of NIC on plasticity in humans and might be relevant for the development of novel nicotinic treatments for cognitive dysfunction. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. In vivo human buccal permeability of nicotine

    DEFF Research Database (Denmark)

    Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

    2006-01-01

    The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non......-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine....... The disappearance rate of nicotine increased significantly as the pH increased, which resulted in P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P...

  7. Nicotine synthesis in Nicotiana tabacum L. induced by mechanical wounding is regulated by auxin.

    Science.gov (United States)

    Shi, Qiumei; Li, Chunjian; Zhang, Fusuo

    2006-01-01

    The effects of different kinds of mechanical wounding on nicotine production in tobacco plants were compared, with sand or hydroponics culture under controlled conditions. Both removal of the shoot apex and damage of the youngest unfolded leaves nos 1 and 2 by a comb-like brusher with 720 punctures caused an increase in nicotine concentration in whole plants at day 3, and reached its highest level at day 6. The nicotine concentration induced by excision of the shoot apex was much higher than that induced by leaf wounding. Both treatments also caused an increase in jasmonic acid (JA) concentration within 90 min in the shoot, followed by an increase in the roots (210 min), in which the JA concentration induced by leaf wounding was significantly higher than that induced by excision of the shoot apex. The increase in nicotine concentration occurred throughout the whole plant, especially in the shoot, while the increase in JA concentration in the shoot was restricted to the damaged tissues, and was not observed in the adjacent tissues. Removal of the lateral buds that emerged after excision of the shoot apex caused a further increase in nicotine concentrations in the plant tissues. Removal of mature leaves, however, did not cause any changes in nicotine concentration in the plant, even though the degree of wounding in this case was comparable with that occurring with apex removal. The results suggest that the nicotine production in tobacco plants was not correlated with the degree of wounding (cut-surface or punctures), but was highly dependent on the removal of apical meristems and hence on the major sources of auxin in the plant. Furthermore, immediate application of 1-naphthylacetic acid (NAA) on the cut surface after removing the shoot apex completely inhibited the increase both in nicotine in whole plants and in JA in the damaged stem segment and roots. Application of an auxin transport inhibitor around the stem directly under the shoot apex of intact plants also

  8. Atitudes dos pneumologistas brasileiros em face da dependência de nicotina: inquérito nacional Attitudes of Brazilian pulmonologists toward nicotine dependence: a national survey

    Directory of Open Access Journals (Sweden)

    Carlos Alberto de Assis Viegas

    2010-04-01

    Full Text Available O tabagismo é uma condição médica por haver dependência de droga, devendo ser abordado por todos os profissionais de saúde como uma doença crônica. Objetivando conhecer a conduta dos pneumologistas brasileiros perante fumantes, realizamos um inquérito nacional, por meio da aplicação de um questionário via internet, enviado para 2.800 desses profissionais, com um retorno de 587 questionários (21%. Observamos que 3,2% dos respondedores não entendem o tabagismo como uma condição médica. Somente 14,7% responderam tratar o tabagismo, e 32,4% disseram encaminhar o fumante para outro colega tratá-lo. Os resultados sugerem que os pneumologistas brasileiros não têm conhecimento suficiente sobre as terapias de cessação do tabagismo.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. Relationship between Personality Traits and Nicotine Dependence in Male and Female Smokers of African-American and European-American Samples

    Directory of Open Access Journals (Sweden)

    Jung-Seok Choi

    2017-07-01

    Full Text Available AimsPersonality characteristics are linked to nicotine dependence (ND. It remains unclear whether these factors differ across African-American (AA and European-American (EA male and female smokers. This study was aimed to determine the relationship between personality traits and smoking status, as well as the degree of ND, in AA and EA male and female samples.MethodsA total of 5,040 participants (AA: N = 3,737, female = 54.31%; EA: N = 1,313, female = 64.51% were included in this study, with 2,474 smokers and 2,566 non-smokers. The measures used in this study included five dimensions of personality by the NEO-personality inventory-revised (neuroticism, extraversion, agreeableness, openness to experience, and conscientiousness, Fagerström test for ND, and drive subscale of the ND Syndrome Scale (NDSS.ResultsIn the AA sample, neuroticism was significantly associated with a higher risk of smoking [odds ratio (OR = 1.057; 95% confidence interval (CI 1.032, 1.083; p < 0.0001], and conscientiousness was significantly associated with decreased risk of smoking (OR = 0.936; 95% CI 0.912, 0.961; p < 0.0001. In the EA sample, higher neuroticism was associated with increased risk of being a current smoker (OR = 1.058; 95% CI 1.013, 1.104; p = 0.0105. Furthermore, we found that a lower level of neuroticism and higher level of conscientiousness were associated with the severity of ND in both the AA and EA samples and a broader range of personality factors were involved in predicting the severity of ND in the AA samples. However, no differential association was detected between male and female smokers of both AA and EA samples.ConclusionThere exist differential relationships between personality traits and the severity of ND in the AA and EA samples.

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

    Science.gov (United States)

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

    2017-05-01

    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.

  11. Monolayer phosphorene under time-dependent magnetic field

    Science.gov (United States)

    Nascimento, J. P. G.; Aguiar, V.; Guedes, I.

    2018-02-01

    We obtain the exact wave function of a monolayer phosphorene under a low-intensity time-dependent magnetic field using the dynamical invariant method. We calculate the quantum-mechanical energy expectation value and the transition probability for a constant and an oscillatory magnetic field. For the former we observe that the Landau level energy varies linearly with the quantum numbers n and m and the magnetic field intensity B0. No transition takes place. For the latter, we observe that the energy oscillates in time, increasing linearly with the Landau level n and m and nonlinearly with the magnetic field. The (k , l) →(n , m) transitions take place only for l = m. We investigate the (0,0) →(n , 0) and (1 , l) and (2 , l) probability transitions.

  12. Testing for cubic smoothing splines under dependent data.

    Science.gov (United States)

    Nummi, Tapio; Pan, Jianxin; Siren, Tarja; Liu, Kun

    2011-09-01

    In most research on smoothing splines the focus has been on estimation, while inference, especially hypothesis testing, has received less attention. By defining design matrices for fixed and random effects and the structure of the covariance matrices of random errors in an appropriate way, the cubic smoothing spline admits a mixed model formulation, which places this nonparametric smoother firmly in a parametric setting. Thus nonlinear curves can be included with random effects and random coefficients. The smoothing parameter is the ratio of the random-coefficient and error variances and tests for linear regression reduce to tests for zero random-coefficient variances. We propose an exact F-test for the situation and investigate its performance in a real pine stem data set and by simulation experiments. Under certain conditions the suggested methods can also be applied when the data are dependent. © 2010, The International Biometric Society.

  13. Restoration of miR-1305 relieves the inhibitory effect of nicotine on periodontal ligament-derived stem cell proliferation, migration, and osteogenic differentiation.

    Science.gov (United States)

    Chen, Zhuo; Liu, Hui-Li

    2017-04-01

    Nicotine hinders the regenerative potentials of human periodontal ligament-derived stem cells (PDLSCs) and delays the healing process of periodontal diseases, but the underlying mechanism remains unclear. miR-1305 upregulation and its potential target RUNX2 downregulation exist in the PDLSCs exposed to nicotine. In this study, we aimed to investigate whether nicotine inhibits PDLSC proliferation, migration, and osteogenic differentiation by increasing miR-1305 level and decreasing RUNX2 level. Quantitative real-time PCR (qRT-PCR) and Western blot assays were performed to detect the expression levels of miR-1305 and RUNX2 in the PDLSCs exposed to nicotine, respectively. PDLSCs with miR-1305 overexpression, low expression, or RUNX2 overexpression were constructed by lipofectin transfection. MTT, migration, and Western blot assays were applied to assess the effect of miR-1305 on PDLSC proliferation, migration, and osteogenic differentiation, respectively. Target prediction and luciferase reporter assays were performed to investigate the targets of miR-1305. Nicotine promoted miR-1305 expression and inhibited RUNX2 expression in PDLSCs. Cell proliferation, migration, and differentiation detection showed that nicotine suppressed proliferation, migration, and osteogenic differentiation of PDLSCs, and restoration of miR-1305 relieved the inhibitory effect of nicotine on PDLSCs. Moreover, we identified and validated that RUNX2 was a direct target of miR-1305, and upregulation of RUNX2 had similar effects with the downregulation of miR-1305 on relieving the inhibitory effect of nicotine on PDLSCs. Nicotine suppresses proliferation, migration, and osteogenic differentiation of PDLSCs, and restoration of miR-1305 relieves the inhibitory effect of nicotine on PDLSCs depending on its target RUNX2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Path dependence of lithium ion cells aging under storage conditions

    Science.gov (United States)

    Su, Laisuo; Zhang, Jianbo; Huang, Jun; Ge, Hao; Li, Zhe; Xie, Fengchao; Liaw, Bor Yann

    2016-05-01

    This work investigates path dependence of lithium ion cells that are stored under static and non-static conditions. In the static storage tests, the levels of temperature and state of charge (SOC) are kept constant. The results of 12 tests from a combination of three temperatures and four SOCs show that, as expected, the cell ages faster at higher temperature and higher SOC. However, the cell aging mode, while consistent for all the evaluated temperatures, is different at 95% SOC from that at lower SOCs. In the non-static storage tests, the levels of temperature and SOC vary with time during the test process. The effect of the sequence of stress levels on cell aging is studied statistically using the statistical method of analysis of variation (ANOVA). It is found that cell capacity fade is path independent of both SOC and temperature, while cell resistance increase is path dependent on SOC and path independent of temperature. Finally, rate-based empirical aging models are adopted to fit the cell aging in the static storage tests. The aging model for capacity fade is demonstrated to be applicable to the non-static tests with errors between -3% and +3% for all the tested conditions over 180 days.

  15. The nicotine dependence associated with alcohol use and other psychoactive substance A dependência da nicotina associada ao uso de álcool e outras substâncias psicoativas

    Directory of Open Access Journals (Sweden)

    Rafaela Serra Bacchi

    2008-10-01

    Full Text Available To examine an association between nicotine dependence with alcohol, other psychoactive use, and depressive disorder. Smokers were recruited from Centro de Referência de Abordagem e Tratamento do Tabagismo at the Hospital das Clínicas da Universidade Estadual de Londrina (AHC/ UEL. All subjects were informed and gave then written consent for the research as approved by the Ethics Research Committee of Universidade Estadual de Londrina. The measures used were: structured questionnaire, alcohol, smoking, and psychoactive substance involvement screening test (ASSIST v 3.0, the Fagerström test for Nicotine Dependence (FTND, and the Diagnostic Interview for Research on Depressive disorder of the World Health Organization. Smokers presented the following socio-demographic characteristics: prevalence of the female sex and mean age of 47 years old with capacity for domestic activities and work. The mean age of onset of cigarette use for smokers was 16 years old. Fagerström’s test presented a medium punctuation of 6, so much for users of substances psicoativas, as for the ones that they don’t use them. Relationship between serious depression and the of psychoactive substances use was relevant for the research. This study evidenced an association among the use of the tobacco and other psychoactive substances, and depressive disorder. The health professional in smoking cessation intervention would be to identify subgroups of adult smokers, associated with depression, psychoactive substance use, and promote an intervention in both comorbidities and larger effectiveness of the smoking cessation. Analisar a associação entre a dependência de nicotina com o uso de álcool, outras substâncias psicoativas e transtorno depressivo. Os tabagistas foram recrutados a partir do Centro de Referência de Abordagem e Tratamento do Tabagismo no Hospital de Clínicas da Universidade Estadual de Londrina (AHC/UEL. Todos os participantes foram informados e

  16. Depression, alcohol use disorders and nicotine dependence among patients at a general hospital Depressão, transtornos decorrentes do uso de álcool e dependência de nicotina no hospital geral

    Directory of Open Access Journals (Sweden)

    Neury José Botega

    2010-09-01

    Full Text Available OBJECTIVE: To determine prevalence rates and identify patient characteristics associated with depression, alcohol use disorders and nicotine dependence among individuals admitted to a general teaching hospital. METHOD: Using the Hospital Anxiety and Depression Scale and Alcohol Use Disorder Identification Test, we assessed 4,352 consecutive medical and surgical patients admitted over a 13-month period. The patients were also asked to report their daily cigarette smoking habits during the last month. Multiple logistic regression analyses were performed, and odds ratios (ORs were calculated. RESULTS: The mean age of the sample was 49.3 years, and 56.6% were male. Prevalence rates of depression, alcohol use disorders and nicotine dependence were, respectively, 14%, 9.8% and 16.9%. In the multivariate analysis, depression was associated with previous suicide attempts (OR = 8.7, lower level of education (OR = 3.6, prior use of psychotropic medications (OR = 3.1, cancer (OR = 1.7 and pain (OR = 1.7. Alcohol use disorders were associated with male sex (OR = 6.3, smoking (OR = 3.5, admission for an external cause of injury, such as a traffic accident (OR = 2.4, and previous suicide attempts (OR = 2.3. Nicotine dependence was associated with alcohol use disorders (OR = 3.4, young adulthood (OR = 2.3, widowhood (OR = 2.2 and previous suicide attempts (OR = 1.8. CONCLUSION: This is the largest sample of medical and surgical patients ever surveyed with standardized screening instruments in a general hospital in Brazil. The high prevalence rates of psychiatric disorders and the profiles of the patients evaluated in this study underscore the need to develop methods that are more effective for detecting and managing such disorders. Hospital admission should be considered a major opportunity for the detection of psychiatric disorders and the subsequent implementation of the appropriate specific treatment strategies.OBJETIVO: Identificar taxas de prevalência e

  17. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

    Science.gov (United States)

    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.

  18. Donepezil, an acetylcholinesterase inhibitor, attenuates nicotine self-administration and reinstatement of nicotine seeking in rats

    Science.gov (United States)

    Kimmey, Blake A.; Rupprecht, Laura E.; Hayes, Matthew R.; Schmidt, Heath D.

    2013-01-01

    Nicotine craving and cognitive impairments represent core symptoms of nicotine withdrawal and predict relapse in abstinent smokers. Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Donepezil is an acetylcholinesterase inhibitor that has been shown previously to improve cognition in healthy non–treatment-seeking smokers. However, there are no studies examining the effects of donepezil on nicotine self-administration and/or the reinstatement of nicotine-seeking behavior in rodents. The present experiments were designed to determine the effects of acute donepezil administration on nicotine taking and the reinstatement of nicotine-seeking behavior, an animal model of relapse in abstinent human smokers. Moreover, the effects of acute donepezil administration on sucrose self-administration and sucrose seeking were also investigated in order to determine whether donepezil's effects generalized to other reinforced behaviors. Acute donepezil administration (1.0 or 3.0 mg/kg, i.p.) attenuated nicotine, but not sucrose self-administration maintained on a fixed-ratio 5 schedule of reinforcement. Donepezil administration also dose-dependently attenuated the reinstatement of both nicotine- and sucrose-seeking behaviors. Commonly reported adverse effects of donepezil treatment in humans are nausea and vomiting. However, at doses required to attenuate nicotine self-administration in rodents, no effects of donepezil on nausea/malaise as measured by pica were observed. Collectively, these results indicate that increased extracellular acetylcholine levels are sufficient to attenuate nicotine taking and seeking in rats and that these effects are not due to adverse malaise symptoms such as nausea. PMID:23231479

  19. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA......). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... are unknown. We addressed this issue by examining the effects of nicotine on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca(2+)-imaging methods in brain slices from mice (P12-P45). Nicotine applied by puffer pipette or bath superfusion elicited membrane...

  20. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    Science.gov (United States)

    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.

  1. Variable effects of nicotine, anabasine, and their interactions on parasitized bumble bees

    Science.gov (United States)

    Thorburn, Lukas P.; Adler, Lynn S.; Irwin, Rebecca E.; Palmer-Young, Evan C.

    2015-01-01

    Secondary metabolites in floral nectar have been shown to reduce parasite load in two common bumble bee species. Previous studies on the effects of nectar secondary metabolites on parasitized bees have focused on single compounds in isolation; however, in nature, bees are simultaneously exposed to multiple compounds. We tested for interactions between the effects of two alkaloids found in the nectar of Nicotiana spp. plants, nicotine and anabasine, on parasite load and mortality in bumble bees ( Bombus impatiens) infected with the intestinal parasite Crithidia bombi. Adult worker bees inoculated with C. bombi were fed nicotine and anabasine diet treatments in a factorial design, resulting in four nectar treatment combinations:  2 ppm nicotine, 5 ppm anabasine, 2ppm nicotine and 5 ppm anabasine together, or a control alkaloid-free solution. We conducted the experiment twice: first, with bees incubated under variable environmental conditions (‘Variable’; temperatures varied from 10-35°C with ambient lighting); and second, under carefully controlled environmental conditions (‘Stable’; 27°C incubator, constant darkness). In ‘Variable’, each alkaloid alone significantly decreased parasite loads, but this effect was not realized with the alkaloids in combination, suggesting an antagonistic interaction. Nicotine but not anabasine significantly increased mortality, and the two compounds had no interactive effects on mortality. In ‘Stable’, nicotine significantly increased parasite loads, the opposite of its effect in ‘Variable’. While not significant, the relationship between anabasine and parasite loads was also positive. Interactive effects between the two alkaloids on parasite load were non-significant, but the pattern of antagonistic interaction was similar to that in the variable experiment. Neither alkaloid, nor their interaction, significantly affected mortality under controlled conditions. Our results do not indicate synergy between Nicotiana

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

    International Nuclear Information System (INIS)

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-01-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

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

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  4. Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor.

    Directory of Open Access Journals (Sweden)

    Atsuo Kawakita

    Full Text Available BACKGROUND: Cigarette smoking adversely affects endochondral ossification during the course of skeletal growth. Among a plethora of cigarette chemicals, nicotine is one of the primary candidate compounds responsible for the cause of smoking-induced delayed skeletal growth. However, the possible mechanism of delayed skeletal growth caused by nicotine remains unclarified. In the last decade, localization of neuronal nicotinic acetylcholine receptor (nAChR, a specific receptor of nicotine, has been widely detected in non-excitable cells. Therefore, we hypothesized that nicotine affect growth plate chondrocytes directly and specifically through nAChR to delay skeletal growth. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of nicotine on human growth plate chondrocytes, a major component of endochondral ossification. The chondrocytes were derived from extra human fingers. Nicotine inhibited matrix synthesis and hypertrophic differentiation in human growth plate chondrocytes in suspension culture in a concentration-dependent manner. Both human and murine growth plate chondrocytes expressed alpha7 nAChR, which constitutes functional homopentameric receptors. Methyllycaconitine (MLA, a specific antagonist of alpha7 nAChR, reversed the inhibition of matrix synthesis and functional calcium signal by nicotine in human growth plate chondrocytes in vitro. To study the effect of nicotine on growth plate in vivo, ovulation-controlled pregnant alpha7 nAChR +/- mice were given drinking water with or without nicotine during pregnancy, and skeletal growth of their fetuses was observed. Maternal nicotine exposure resulted in delayed skeletal growth of alpha7 nAChR +/+ fetuses but not in alpha7 nAChR -/- fetuses, implying that skeletal growth retardation by nicotine is specifically mediated via fetal alpha7 nAChR. CONCLUSIONS/SIGNIFICANCE: These results suggest that nicotine, from cigarette smoking, acts directly on growth plate chondrocytes to decrease

  5. Hormones, Nicotine and Cocaine: Clinical Studies

    Science.gov (United States)

    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 (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

  6. Urine nicotine metabolites and smoking behavior in a multiracial/multiethnic national sample of young adults.

    Science.gov (United States)

    Kandel, Denise B; Hu, Mei-Chen; Schaffran, Christine; Udry, J Richard; Benowitz, Neal L

    2007-04-15

    Nicotine metabolism has been hypothesized to affect patterns of smoking. The recent development of a noninvasive measure of nicotine metabolism, the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine), makes it possible to examine the association between rate of nicotine metabolism and smoking behavior in the general population. This US study examined group differences in the ratio measured in urine and the association between the ratio and multiple measures of smoking behavior and nicotine dependence in a large, national representative sample of young adults. The sample included 900 daily smokers aged 18-26 years from wave III (2001-2002) of the National Longitudinal Survey of Adolescent Health. Nicotine dependence was measured by using the Fagerström Test for Nicotine Dependence. Females had higher nicotine metabolite ratios than males; Whites and Hispanics had higher nicotine metabolite ratios than African Americans or Asians. This finding is consistent with those from laboratory studies of older smokers based on intravenous infusion of nicotine. No significant association was found between the nicotine metabolite ratio and number of cigarettes smoked per day or nicotine dependence. The availability of a noninvasive measure makes possible systematic testing of causal hypotheses generated by laboratory studies in the general population.

  7. Alpha5 nicotinic acetylcholine receptor mediates nicotine-induced HIF-1α and VEGF expression in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Ma, Xiaoli; Jia, Yanfei; Zu, Shanshan; Li, Ruisheng; Jia, Ying; Zhao, Yun; Xiao, Dongjie; Dang, Ningning; Wang, Yunshan

    2014-01-01

    By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and apoptosis of non-small cell lung cancer (NSCLC). Previous studies have indicated that α5-nAChR is highly associated with lung cancer risk and nicotine dependence. However, the mechanisms through which α5-nAChRs may influence lung carcinogenesis are far from clear. In the present study, we investigated the roles of α5-nAChR in the nicotine-induced expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Immunohistochemistry was used to detect the expression of α5-nAChR and HIF-1α in 60 specimens of lung cancer and para-carcinoma tissue. The correlations between the expression levels of α5-nAChR and HIF-1α and other clinicopathological data were analyzed. In a cell line that highly expressed α5-nAChR, the loss of α5-nAChR function by siRNA was used to study whether α5-nAChR is involved in the nicotine-induced expression of HIF-1α and VEGF through the activation of the ERK1/2 and PI3K/Akt signaling pathways. Cell growth was detected using the cell counting kit-8 (CCK-8). α5-nAChR (78.3%) and HIF-1α (88.3%) were both overexpressed in NSCLC, and their expression levels were found to be correlated with each other (P < 0.05). In the A549 cell line, α5-nAChR and HIF-1α were found to be expressed under normal conditions, and their expression levels were significantly increased in response to nicotine treatment. The silencing of α5-nAChR significantly inhibited the nicotine-induced cell proliferation compared with the control group and attenuated the nicotine-induced upregulation of HIF-1α and VEGF, and these effects required the cooperation of the ERK1/2 and PI3K/Akt signaling pathways. These results show that the α5-nAChR/HIF-1α/VEGF axis is involved in nicotine-induced tumor cell proliferation, which suggests that α5-nAChR may serve as a potential anticancer target in nicotine-associated lung cancer. - Highlights

  8. Alpha5 nicotinic acetylcholine receptor mediates nicotine-induced HIF-1α and VEGF expression in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Xiaoli; Jia, Yanfei; Zu, Shanshan [Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China); Li, Ruisheng [Institute of Infectious Diseases, 302 Military Hospital, Beijing 100039 (China); Jia, Ying; Zhao, Yun; Xiao, Dongjie [Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China); Dang, Ningning [Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China); Wang, Yunshan [Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China)

    2014-07-15

    By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and apoptosis of non-small cell lung cancer (NSCLC). Previous studies have indicated that α5-nAChR is highly associated with lung cancer risk and nicotine dependence. However, the mechanisms through which α5-nAChRs may influence lung carcinogenesis are far from clear. In the present study, we investigated the roles of α5-nAChR in the nicotine-induced expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Immunohistochemistry was used to detect the expression of α5-nAChR and HIF-1α in 60 specimens of lung cancer and para-carcinoma tissue. The correlations between the expression levels of α5-nAChR and HIF-1α and other clinicopathological data were analyzed. In a cell line that highly expressed α5-nAChR, the loss of α5-nAChR function by siRNA was used to study whether α5-nAChR is involved in the nicotine-induced expression of HIF-1α and VEGF through the activation of the ERK1/2 and PI3K/Akt signaling pathways. Cell growth was detected using the cell counting kit-8 (CCK-8). α5-nAChR (78.3%) and HIF-1α (88.3%) were both overexpressed in NSCLC, and their expression levels were found to be correlated with each other (P < 0.05). In the A549 cell line, α5-nAChR and HIF-1α were found to be expressed under normal conditions, and their expression levels were significantly increased in response to nicotine treatment. The silencing of α5-nAChR significantly inhibited the nicotine-induced cell proliferation compared with the control group and attenuated the nicotine-induced upregulation of HIF-1α and VEGF, and these effects required the cooperation of the ERK1/2 and PI3K/Akt signaling pathways. These results show that the α5-nAChR/HIF-1α/VEGF axis is involved in nicotine-induced tumor cell proliferation, which suggests that α5-nAChR may serve as a potential anticancer target in nicotine-associated lung cancer. - Highlights

  9. Antifungal activity of nicotine and its cadmium complex

    International Nuclear Information System (INIS)

    Zaidi, I.M.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Cd(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activities against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cadmium(II) iodide was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine is quite effective against the rare pathogenic and Non pathogenic fungi but comparatively less effective against Pathogenic fungi. Nicotine was found to be completely ineffective against the selected species of Occasional pathogenic fungi. Cadmium(II) iodide effectively inhibited Pathogenic and Non pathogenic fungi whereas relatively ineffective against the Occasional pathogenic and Rare pathogenic fungi. On the other hand, Cadmium(II) nicotine complex inhibited all the selected species of fungi except Fusarium solani. (author)

  10. Cigarette nicotine yields and nicotine intake among Japanese male workers

    OpenAIRE

    Ueda, K; Kawachi, I; Nakamura, M; Nogami, H; Shirokawa, N; Masui, S; Okayama, A; Oshima, A

    2002-01-01

    Objectives: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding ≤ 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers.

  11. A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

    Science.gov (United States)

    Patten, Christi A.

    2000-01-01

    Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

  12. Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

    Science.gov (United States)

    Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

    2016-11-01

    Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

  13. Optimizing cholinergic tone through lynx modulators of nicotinic receptors: implications for plasticity and nicotine addiction.

    Science.gov (United States)

    Miwa, Julie M; Lester, Henry A; Walz, Andreas

    2012-08-01

    The cholinergic system underlies both adaptive (learning and memory) and nonadaptive (addiction and dependency) behavioral changes through its ability to shape and regulate plasticity. Protein modulators such as lynx family members can fine tune the activity of the cholinergic system and contribute to the graded response of the cholinergic system, stabilizing neural circuitry through direct interaction with nicotinic receptors. Release of this molecular brake can unmask cholinergic-dependent mechanisms in the brain. Lynx proteins have the potential to provide top-down control over plasticity mechanisms, including addictive propensity. If this is indeed the case, then, what regulates the regulator? Transcriptional changes of lynx genes in response to pharmacological, physiological, and pathological alterations are explored in this review.

  14. Reduced nicotine content cigarettes in smokers of low socioeconomic status: study protocol for a randomized control trial.

    Science.gov (United States)

    Krebs, Nicolle M; Allen, Sophia I; Veldheer, Susan; Martinez, Diane J; Horn, Kimberly; Livelsberger, Craig; Modesto, Jennifer; Kuprewicz, Robin; Wilhelm, Ashley; Hrabovsky, Shari; Kazi, Abid; Fazzi, Alyse; Liao, Jason; Zhu, Junjia; Wasserman, Emily; Reilly, Samantha M; Reinhart, Lisa; Trushin, Neil; Moyer, Robinn E; Bascom, Rebecca; Foulds, Jonathan; Richie, John P; Muscat, Joshua E

    2017-07-03

    The Family Smoking Prevention and Tobacco Control Act gave the Food and Drug Administration jurisdiction over the regulation of all tobacco products, including their nicotine content. Under this act, a major strategy to reduce harm from cigarette tobacco is lowering the nicotine content without causing unintended adverse consequences. Initial research on reduced nicotine content (RNC) cigarettes has shown that smokers of these cigarettes gradually decrease their smoking frequency and biomarkers of exposure. The effectiveness of this strategy needs to be demonstrated in different populations whose response to RNC cigarettes might be substantially mediated by personal or environmental factors, such as low socioeconomic status (SES) populations. This study aims to evaluate the response to a reduced nicotine intervention in low SES smokers, as defined here as those with less than 16 years of education, by switching smokers from high nicotine commercial cigarettes to RNC cigarettes. Adults (N = 280) who have smoked five cigarettes or more per day for the past year, have not made a quit attempt in the prior month, are not planning to quit, and have less than 16 years of education are recruited into a two-arm, double-blinded randomized controlled trial. First, participants smoke their usual brand of cigarettes for 1 week and SPECTRUM research cigarettes containing a usual amount of nicotine for 2 weeks. During the experimental phase, participants are randomized to continue smoking SPECTRUM research cigarettes that contain either (1) usual nicotine content (UNC) (11.6 mg/cigarette) or (2) RNC (11.6 to 0.2 mg/cigarette) over 18 weeks. During the final phase of the study, all participants are offered the choice to quit smoking with nicotine replacement therapy, continue smoking the research cigarettes, or return to their usual brand of cigarettes. The primary outcomes of the study include retention rates and compliance with using only research cigarettes and no

  15. Addiction Potential of Cigarettes With Reduced Nicotine Content in Populations With Psychiatric Disorders and Other Vulnerabilities to Tobacco Addiction.

    Science.gov (United States)

    Higgins, Stephen T; Heil, Sarah H; Sigmon, Stacey C; Tidey, Jennifer W; Gaalema, Diann E; Hughes, John R; Stitzer, Maxine L; Durand, Hanna; Bunn, Janice Y; Priest, Jeff S; Arger, Christopher A; Miller, Mollie E; Bergeria, Cecilia L; Davis, Danielle R; Streck, Joanna M; Reed, Derek D; Skelly, Joan M; Tursi, Lauren

    2017-10-01

    A national policy is under consideration to reduce the nicotine content of cigarettes to lower nicotine addiction potential in the United States. To examine how smokers with psychiatric disorders and other vulnerabilities to tobacco addiction respond to cigarettes with reduced nicotine content. A multisite, double-blind, within-participant assessment of acute response to research cigarettes with nicotine content ranging from levels below a hypothesized addiction threshold to those representative of commercial cigarettes (0.4, 2.3, 5.2, and 15.8 mg/g of tobacco) at 3 academic sites included 169 daily smokers from the following 3 vulnerable populations: individuals with affective disorders (n = 56) or opioid dependence (n = 60) and socioeconomically disadvantaged women (n = 53). Data were collected from March 23, 2015, through April 25, 2016. After a brief smoking abstinence, participants were exposed to the cigarettes with varying nicotine doses across fourteen 2- to 4-hour outpatient sessions. Addiction potential of the cigarettes was assessed using concurrent choice testing, the Cigarette Purchase Task (CPT), and validated measures of subjective effects, such as the Minnesota Nicotine Withdrawal Scale. Among the 169 daily smokers included in the analysis (120 women [71.0%] and 49 men [29.0%]; mean [SD] age, 35.6 [11.4] years), reducing the nicotine content of cigarettes decreased the relative reinforcing effects of smoking in all 3 populations. Across populations, the 0.4-mg/g dose was chosen significantly less than the 15.8-mg/g dose in concurrent choice testing (mean [SEM] 30% [0.04%] vs 70% [0.04%]; Cohen d = 0.40; P nicotine content cigarettes could be reversed by increasing the response cost necessary to obtain the higher dose (mean [SEM], 61% [0.02%] vs 39% [0.02%]; Cohen d = 0.40; P Nicotine Withdrawal Scale total scores (range of mean decreases, 0.10-0.50; Cohen d range, 0.21-1.05; P nicotine content of cigarettes may decrease

  16. Habenular expression of rare missense variants of the β4 nicotinic receptor subunit alters nicotine consumption

    Directory of Open Access Journals (Sweden)

    Marta A Ślimak

    2014-01-01

    Full Text Available The CHRNA5-CHRNA3-CHRNB4 gene cluster, encoding the α5, α3 and β4 nicotinic acetylcholine receptor (nAChR subunits, has been linked to nicotine dependence. The habenulo-interpeduncular (Hb-IPN tract is particularly enriched in α3β4 nAChRs. We recently showed that modulation of these receptors in the medial habenula (MHb in mice altered nicotine consumption. Given that β4 is rate-limiting for receptor activity and that single nucleotide polymorphisms (SNPs in CHRNB4 have been linked to altered risk of nicotine dependence in humans, we were interested in determining the contribution of allelic variants of β4 to nicotine receptor activity in the MHb. We screened for missense SNPs with allele frequencies > 0.0005 and introduced the corresponding substitutions in Chrnb4. Fourteen variants were analyzed by co-expression with α3. We found that β4A90I and β4T374I variants, previously shown to associate with reduced risk of smoking, and an additional variant β4D447Y, significantly increased nicotine-evoked current amplitudes, while β4R348C, the mutation most frequently encountered in sporadic amyotrophic lateral sclerosis (sALS, showed reduced nicotine currents. We employed lentiviruses to express β4 or β4 variants in the MHb. Immunoprecipitation studies confirmed that β4 lentiviral-mediated expression leads to specific upregulation of α3β4 but not β2 nAChRs in the Mhb. Mice injected with the β4-containing virus showed pronounced aversion to nicotine as previously observed in transgenic Tabac mice overexpressing Chrnb4 at endogenous sites including the MHb. Habenular expression of the β4 gain-of-function allele T374I also resulted in strong aversion, while transduction with the β4 loss-of function allele R348C failed to induce nicotine aversion. Altogether, these data confirm the critical role of habenular β4 in nicotine consumption, and identify specific SNPs in CHRNB4 that modify nicotine-elicited currents and alter nicotine

  17. Characterizing QALYs under a General Rank Dependent Utility Model

    NARCIS (Netherlands)

    H. Bleichrodt (Han); J. Quiggin (John)

    1997-01-01

    textabstractThis paper provides a characterization of QALYs, the most important outcome measure in medical decision making, in the context of a general rank dependent utility model. We show that both for chronic and for nonchronic health states the characterization of QALYs depends on intuitive

  18. Intravenous nicotine self-administration and cue-induced reinstatement in mice: Effects of nicotine dose, rate of drug infusion and prior instrumental training

    Science.gov (United States)

    Fowler, Christie D.; Kenny, Paul J.

    2011-01-01

    Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128

  19. Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

    Science.gov (United States)

    Yan, Yijin; Pushparaj, Abhiram; Le Strat, Yann; Gamaleddin, Islam; Barnes, Chanel; Justinova, Zuzana; Goldberg, Steven R; Le Foll, Bernard

    2012-01-01

    Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue- or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse. PMID:22030716

  20. Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications.

    Science.gov (United States)

    D'Souza, Manoranjan S

    2016-01-01

    Morbidity and mortality associated with tobacco smoking constitutes a significant burden on healthcare budgets all over the world. Therefore, promoting smoking cessation is an important goal of health professionals and policy makers throughout the world. Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco. A majority of the currently available FDA-approved smoking cessation medications act via neuronal nicotinic receptors. These medications are effective in approximately half of all the smokers, who want to quit and relapse among abstinent smokers continues to be high. In addition to relapse among abstinent smokers, unpleasant effects associated with nicotine withdrawal are a major motivational factor in continued tobacco smoking. Over the last two decades, animal studies have helped in identifying several neural substrates that are involved in nicotine-dependent behaviors including those associated with nicotine withdrawal and relapse to tobacco smoking. In this review, first the role of specific brain regions/circuits that are involved in nicotine dependence will be discussed. Next, the review will describe the role of specific nicotinic receptor subunits in nicotine dependence. Finally, the review will discuss the role of classical neurotransmitters (dopamine, serotonin, noradrenaline, glutamate, and γ-aminobutyric acid) as well as endogenous opioid and endocannabinoid signaling in nicotine dependence. The nicotinic and nonnicotinic neural substrates involved in nicotine-dependent behaviors can serve as possible targets for future smoking cessation medications. © 2016 Elsevier B.V. All rights reserved.

  1. Stimulation of Na+ -K+ -pump currents by epithelial nicotinic receptors in rat colon.

    Science.gov (United States)

    Bader, Sandra; Lottig, Lena; Diener, Martin

    2017-05-01

    Acetylcholine-induced epithelial Cl - secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data have shown expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl - secretion by nicotine, in the presence of the neurotoxin, tetrodotoxin. Here, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport. Ussing chamber experiments were performed, using rat distal colon with intact epithelia. Epithelia were basolaterally depolarized to measure currents across the apical membrane. Apically permeabilized tissue was also used to measure currents across the basolateral membrane in the presence of tetrodotoxin. Nicotine had no effect on currents through Cl - channels in the apical membrane or on currents through K + channels in the apical or the basolateral membrane. Instead, nicotine stimulated the Na + -K + -pump as indicated by Na + -dependency and sensitivity of the nicotine-induced current across the basolateral membrane to cardiac steroids. Effects of nicotine were inhibited by nicotinic receptor antagonists such as hexamethonium and mimicked by dimethyl-4-phenylpiperazinium, a chemically different nicotinic agonist. Simultaneous stimulation of epithelial muscarinic and nicotinic receptors led to a strong potentiation of transepithelial Cl - secretion. These results suggest a novel concept for the cholinergic regulation of transepithelial ion transport by costimulation of muscarinic and nicotinic epithelial receptors and a unique role of nicotinic receptors controlling the activity of the Na + -K + -ATPase. © 2017 The British Pharmacological Society.

  2. Nicotine increases sucrose self-administration and seeking in rats.

    Science.gov (United States)

    Grimm, Jeffrey W; Ratliff, Christine; North, Kindsey; Barnes, Jesse; Collins, Stefan

    2012-05-01

    Associations between nicotine in cigarettes and food consumption may alter the incentive value of food such that food cue-reactivity is exaggerated during abstinence from smoking. This effect may contribute to the weight gain associated with cessation of smoking. We examined the effects of nicotine (0.4 mg/kg base subcutaneous) paired (NPD) or unpaired (NUP) with 10% sucrose self-administration (SA; 0.2 ml/delivery, 1 h/day for 10 days) on SA response rate and intake as well as sucrose cue-reactivity following either 1 or 30 days of forced abstinence. Rats were administered the training dose of nicotine prior to a second, consecutive cue-reactivity session. NPD rats responded at over three times the rate for sucrose and earned nearly twice the number of sucrose deliveries as NUP rats or saline controls. Sucrose cue-reactivity was greater after 30 days versus 1 day of forced abstinence for all groups. History of nicotine exposure had no effect on sucrose cue-reactivity. However, the subsequent injection of nicotine increased sucrose cue-reactivity only in the NPD groups. There were no abstinent-dependent effects of nicotine challenge on sucrose cue-reactivity. A study conducted in parallel with water as the reinforcer revealed a less dramatic effect of nicotine on intake. There was no history or abstinence-dependent effects of nicotine on water cue-reactivity. Nicotine increases the reinforcing effects of sucrose and sucrose-paired cues when nicotine is present. An implication of these findings is that relapse to nicotine (cigarettes) could substantially elevate food cue-reactivity. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  3. Testing the Mean of a Normal Population Under Dependence

    NARCIS (Netherlands)

    Albers, Willem/Wim

    1978-01-01

    Modifications of the $t$-test are considered which are robust under certain violations of the independence assumption. The additional number of observations these modified tests require in order to obtain under independence the same power as the $t$-test, is obtained asymptotically.

  4. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    International Nuclear Information System (INIS)

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

    2014-01-01

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC 50 was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress

  5. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl

    2014-10-15

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

  6. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...

  7. T100. NICOTINE USE IMPACTS NEGATIVE SYMPTOMS SEVERITY IN SCHIZOPHRENIA

    Science.gov (United States)

    Oliveira, Hianna; Coutinho, Luccas; Higuchi, Cinthia; Noto, Cristiano; Bressan, Rodrigo; Gadelha, Ary

    2018-01-01

    Abstract Background Nicotine use is higher among patients with schizophrenia (50–98%) than in general population (25–30%). This association can reflect a non-specific liability to substance use or specific effects of tobacco on symptoms severity or side effects. Studies about nicotine use and schizophrenia symptoms dimensions are controversial. Some of them showed a relation between severe nicotine use and higher positive symptoms and others presented a correlation between lower negative symptoms and nicotine use. That is why we aimed to verify whether nicotine use is associated with symptoms dimensions in patients with schizophrenia. Methods Two hundred and seven outpatients were enrolled from the Programa de Esquizofrenia da Universidade Federal de São Paulo (PROESQ/UNIFESP). Schizophrenia diagnosis was confirmed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Dimensional psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS) and Fagerstrom Test for Nicotine Dependence. The PANSS items were grouped in five dimensions: positive, negative, disorganized/cognitive, mood/depression and excitement/hostility. The total score of Fagerstrom Test for Nicotine Dependence was the index used for severity in nicotine dependence. We used Wilcoxon-mann- whitney test to compare the means of PANSS dimensions between nicotine users versus non nicotine use. Results The patients mean age was 36.75 (SD 10.648), 69.1% were male, 48.3% reported lifetime tobacco use and 34.3% reported current tobacco use. Lower scores on negative dimension were associated with nicotine use (W = 5642.5, p-value = 0.046, effect size = 0.446). All p-values were corrected by Bonferroni test. Tests that evaluated the relationship between nicotine use and the total PANSS score or other dimensions were not statistically significant. Discussion This study shows that nicotine use impacts negative symptoms of schizophrenia. Increase in hepatic metabolism leading

  8. Graphical models for inference under outcome-dependent sampling

    DEFF Research Database (Denmark)

    Didelez, V; Kreiner, S; Keiding, N

    2010-01-01

    We consider situations where data have been collected such that the sampling depends on the outcome of interest and possibly further covariates, as for instance in case-control studies. Graphical models represent assumptions about the conditional independencies among the variables. By including...

  9. Electronic cigarette user plasma nicotine concentration, puff topography, heart rate, and subjective effects: Influence of liquid nicotine concentration and user experience.

    Science.gov (United States)

    Hiler, Marzena; Breland, Alison; Spindle, Tory; Maloney, Sarah; Lipato, Thokozeni; Karaoghlanian, Nareg; Shihadeh, Alan; Lopez, Alexa; Ramôa, Carolina; Eissenberg, Thomas

    2017-10-01

    Electronic cigarette (ECIG) nicotine delivery and other effects may depend on liquid nicotine concentration and user experience. This study is the first to systematically examine the influence of ECIG liquid nicotine concentration and user experience on nicotine delivery, heart rate, puff topography, and subjective effects. Thirty-three ECIG-experienced individuals and 31 ECIG-naïve cigarette smokers completed 4 laboratory conditions consisting of 2, 10-puff bouts (30-sec interpuff interval) with a 3.3-V ECIG battery attached to a 1.5-Ω "cartomizer" (7.3 W) filled with 1 ml ECIG liquid. Conditions differed by liquid nicotine concentration: 0, 8, 18, or 36 mg/ml. Participants' plasma nicotine concentration was directly related to liquid nicotine concentration and dependent on user experience, with significantly higher mean plasma nicotine increases observed in ECIG-experienced individuals relative to ECIG-naïve smokers in each active nicotine condition. When using 36 mg/ml, mean plasma nicotine increase for ECIG-experienced individuals was 17.9 ng/ml (SD = 17.2) and 6.9 (SD = 7.1; p users: collapsed across condition, mean puff duration was 5.6 sec (SD = 3.0) for ECIG-experienced and 2.9 (SD = 1.5) for ECIG-naïve individuals. ECIG use also suppressed nicotine/tobacco abstinence symptoms in both groups; the magnitude of abstinence symptom suppression depended on liquid nicotine concentration and user experience. These and other recent results suggest that policies intended to limit ECIG nicotine delivery will need to account for factors in addition to liquid nicotine concentration (e.g., device power and user behavior). (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. THE EFFECTS OF NICOTINE TREATMENT ON THE ANTIOXIDANT ENZIMES ACTIVITY IN THE RAT BRAIN

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-12-01

    Full Text Available Nicotine has been reported to be therapeutic in some patients with certain neurodegenerative diseases and to have neuroprotective effects in the central nervous system. However, nicotine administration may result in oxidative stress by inducing the generation of reactive oxygen species in the periphery and central nervous system. There is also evidence suggesting that nicotine may have antioxidant properties in the central nervous system. The antioxidant properties of nicotine may be intracellular through the activation of the nicotinic receptors or extracellular by acting as a radical scavenger in that it binds to iron. The possibility that nicotine might be used to treat some symptoms of certain neurodegenerative diseases underlies the necessity to determine whether nicotine has pro-oxidant, antioxidant or properties of both. In the present study we evaluated the effects of nicotine treatment (0.3 mg/kg g.c., i.p., SIGMA, 7 continuous days administration, on the antioxidant enzymes activity.

  11. Nicotine inhibits memory CTL programming.

    Directory of Open Access Journals (Sweden)

    Zhifeng Sun

    Full Text Available Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development.

  12. Neural mechanisms underlying context-dependent shifts in risk preferences

    NARCIS (Netherlands)

    Losecaat Vermeer, A.B.; Boksem, M.A.S.; Sanfey, A.G.

    2014-01-01

    Studies of risky decision-making have demonstrated that humans typically prefer risky options after incurring a financial loss, while generally preferring safer options after a monetary gain. Here, we examined the neural processes underlying these inconsistent risk preferences by investigating the

  13. Insight into nicotine addiction

    Directory of Open Access Journals (Sweden)

    Sahil Handa

    2017-01-01

    Full Text Available The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.

  14. Historical and current perspective on tobacco use and nicotine addiction.

    Science.gov (United States)

    Dani, John A; Balfour, David J K

    2011-07-01

    Although the addictive influence of tobacco was recognized very early, the modern concepts of nicotine addiction have relied on knowledge of cholinergic neurotransmission and nicotinic acetylcholine receptors (nAChRs). The discovery of the 'receptive substance' by Langley, that would turn out to be nAChRs, and 'Vagusstoff' (acetylcholine) by Loewi, coincided with an exciting time when the concept of chemical synaptic transmission was being formulated. More recently, the application of more powerful techniques and the study of animal models that replicate key features of nicotine dependence have led to important advancements in our understanding of molecular, cellular and systems mechanisms of nicotine addiction. In this review, we present a historical perspective and overview of the research that has led to our present understanding of nicotine addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-10-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    International Nuclear Information System (INIS)

    Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

    2016-01-01

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  17. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: kanda@nihs.go.jp [Division of Pharmacology, National Institute of Health Sciences (Japan)

    2016-02-05

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  18. Nicotine metabolism and addiction among adolescent smokers.

    Science.gov (United States)

    Rubinstein, Mark L; Shiffman, Saul; Moscicki, Anna-Barbara; Rait, Michelle A; Sen, Saunak; Benowitz, Neal L

    2013-02-01

    The purpose of this study was to determine the association between the nicotine metabolic rate and smoking behavior, including addiction, in adolescent smokers. Baseline data from a prospective study of adolescent smoking behaviors and nicotine metabolism. The setting was an out-patient university hospital in San Francisco. Adolescent smokers (n = 164) aged 13-17 years old. Participants completed self-report measures of smoking behavior and nicotine dependence (modified Fagerström Tolerance Questionnaire: mFTQ). The nicotine metabolite ratio (NMR), a phenotypic marker of the rate of nicotine metabolism, was calculated using the ratio of concentrations of deuterium-labeled 3'-hydroxycotinine to cotinine-d(4) . Participants reported smoking a mean of 2.86 cigarettes per day (CPD) [median = 1.78, standard deviation (SD) = 3.35] for 1.37 years (median = 1.0, SD = 1.36). Results from multivariate analyses accounting for age, race/ethnicity, gender and duration of smoking indicated that slower metabolizers smoked more CPD than faster metabolizers (the NMR was inversely related to CPD; P = 0.02). Slower metabolizers also showed greater dependence on the mFTQ (NMR was negatively associated with the mFTQ; P = 0.02). In adolescence, slower clearance of nicotine may be associated with greater levels of addiction, perhaps mediated by a greater number of cigarettes smoked. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  19. Nicotine effects on general semantic priming in Parkinson's disease.

    Science.gov (United States)

    Holmes, Anna D; Copland, David A; Silburn, Peter A; Chenery, Helen J

    2011-06-01

    In young healthy nonsmokers, effects of nicotine on semantic processing have been observed under strategy-based priming procedures but not under more general priming procedures (Holmes, Chenery, & Copland, 2008; Holmes, Chenery, & Copland, 2010). Effects of nicotine under general priming procedures, however, may be mediated by baseline priming levels that are below optimum such as when compromised by disease. Nicotinic mechanisms may be involved in the cognitive sequalae of Parkinson's disease (PD). Evidence suggests that semantic processing may be compromised in PD but the potential benefit of nicotinic stimulation is unknown. This study investigated the effects of nicotine on semantic processing in nonsmokers with PD (n = 12) and nonsmoking matched controls (n = 17) using general priming procedures. Specifically, an automatic priming task (0.15 relatedness proportion, RP, and 200 ms stimulus onset asynchrony, SOA) and a controlled priming task (0.8 RP and 1000 ms SOA) were used. Prime-target category relation (category related, noncategory related) was also manipulated. Transdermal nicotine patches (7 mg/24 h) were administered in a double-blind, placebo-controlled, crossover design. For the automatic task, nicotine did not influence priming effects for PD. Unexpectedly, compromised automatic priming for controls was ameliorated. For the controlled task, nicotine influenced priming effects for PD but not controls. The patterns of priming and nicotine effects across the tasks suggest an age-related slowing of the rate of semantic activation for controls, which may be exacerbated in PD. Overall, the findings indicate that nicotine can improve compromised semantic processing in PD, and also influence semantic processing in healthy older individuals. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  20. Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

    OpenAIRE

    Portugal, George S.; Gould, Thomas J.

    2008-01-01

    Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

  1. Political Journalism under Pressure - Between Autonomy and Dependence

    Directory of Open Access Journals (Sweden)

    Günther Pallaver

    2010-06-01

    Full Text Available Dieser Beitrag befasst sich mit der zunehmenden Tendenz politischer Eliten, auf die journalistische Berichterstattung und den politischen Journalismus Einfluss zu nehmen. Dabei wird gezeigt, inwieweit dadurch Handlungsspielräume im politischen Journalismus eingeschränkt werden. Untersucht werden insgesamt vier Länder, nämlich die USA, die Bundesrepublik Deutschland, Österreich und Italien. Beim diesem Vergleich stellt sich die Frage nach der Bedeutung struktureller Unterschiede angesichts der verschiedenen politischen Systeme in den untersuchten Ländern (z. B. präsidentielles vs. parlamentarische Systeme, parteien- vs. medienzentrierte Systeme. Abschließend geht es um Überlegungen zu unterschiedlichen privatrechtlich organisierten oder dualen Mediensystemen im Zusammenhang strategischer Einflussnahmen und Abwehrmaßnahmen. In this paper the proposition to be tested is whether the political elites’ attempt to exert influence on day-to-day news coverage and thus on political journalism is increasing and whether as a result political journalism’s autonomous leeway is continually diminishing. The countries examined are the United States, Germany, Austria and Italy. In this context the question whether there are structural differences due to the diverse political systems of the countries under consideration (presidential vs. parliamentary systems; systems centred more on parties vs. systems centred more on the media will also be investigated. Last but not least, the role of different media systems will be considered, too (media under private law, dual systems including the Italian version.

  2. In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

    International Nuclear Information System (INIS)

    Kassiou, Michael; Eberl, Stefan; Meikle, Steven R.; Birrell, Alex; Constable, Chris; Fulham, Michael J.; Wong, Dean F.; Musachio, John L.

    2001-01-01

    To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[ 123 I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[ 123 I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V d ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V d was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V d or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

  3. Neuronal effects of nicotine during auditory selective attention.

    Science.gov (United States)

    Smucny, Jason; Olincy, Ann; Eichman, Lindsay S; Tregellas, Jason R

    2015-06-01

    Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.

  4. The Metabotropic Glutamate 2/3 Receptor Agonist LY379268 Blocked Nicotine-Induced Increases in Nucleus Accumbens Shell Dopamine only in the Presence of a Nicotine-Associated Context in Rats

    Science.gov (United States)

    D'Souza, Manoranjan S; Liechti, Matthias E; Ramirez-Niño, Ana M; Kuczenski, Ronald; Markou, Athina

    2011-01-01

    The metabotropic glutamate 2/3 (mGlu2/3) receptor agonist LY379268 ([−]-2-oxa-4-aminobicyclo [3.1.0] hexane-4,6-dicarboxylate) attenuates both nicotine self-administration and cue-induced nicotine seeking in rats. In this study, the effects of LY379268 (1 mg/kg) or saline pretreatment on nicotine-induced increases in nucleus accumbens (NAcc) shell dopamine were evaluated using in vivo microdialysis under different experimental conditions: (i) nicotine (0.4 mg/kg, base) was experimenter-administered subcutaneously to nicotine-naïve rats; (ii) nicotine was experimenter-administered either subcutaneously (0.4 mg/kg) or by a single experimenter-administered infusion (0.06 mg/kg, base) in rats with a history of nicotine self-administration (nicotine experienced) in the absence of a nicotine-associated context (ie, context and cues associated with nicotine self-administration); (iii) nicotine (0.06 mg/kg) was self-administered or experimenter-administered in nicotine-experienced rats in the presence of a nicotine-associated context. In saline-pretreated nicotine-naïve and nicotine-experienced rats, nicotine increased NAcc shell dopamine regardless of the context used for testing. Interestingly, LY379268 pretreatment blocked nicotine-induced increases in NAcc shell dopamine in nicotine-experienced rats only when tested in the presence of a nicotine-associated context. LY379268 did not block nicotine-induced increases in NAcc shell dopamine in nicotine-naïve or -experienced rats tested in the absence of a nicotine-associated context. These intriguing findings suggest that activation of mGlu2/3 receptors negatively modulates the combined effects of nicotine and nicotine-associated contexts/cues on NAcc dopamine. Thus, these data highlight a critical role for mGlu2/3 receptors in context/cue-induced drug-seeking behavior and suggest a neurochemical mechanism by which mGlu2/3 receptor agonists may promote smoking cessation by preventing relapse induced by the

  5. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  6. Antifungal activity of nicotine and its cobalt complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Co(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activity against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cobalt(II) chloride was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine had antifungal activity against all species of fungi studied except Candida albicans, Microsporum canis, Epidermophyton floccosum, Candida tropicalis, and Alternaria infectoria. Cobalt(II) nicotine was found to be effective against all selected species of fungi but ineffective against Candida solani, Penicillium notalum, Microsporum canis, Fusarium solani and Fusarium moniliforme. (author)

  7. Variable effects of nicotine, anabasine, and their interactions on parasitized bumble bees [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Lukas P. Thorburn

    2015-12-01

    Full Text Available Secondary metabolites in floral nectar have been shown to reduce parasite load in two common bumble bee species. Previous studies on the effects of nectar secondary metabolites on parasitized bees have focused on single compounds in isolation; however, in nature, bees are simultaneously exposed to multiple compounds. We tested for interactions between the effects of two alkaloids found in the nectar of Nicotiana spp. plants, nicotine and anabasine, on parasite load and mortality in bumble bees (Bombus impatiens infected with the intestinal parasite Crithidia bombi. Adult worker bees inoculated with C. bombi were fed nicotine and anabasine diet treatments in a factorial design, resulting in four nectar treatment combinations:  2 ppm nicotine, 5 ppm anabasine, 2ppm nicotine and 5 ppm anabasine together, or a control alkaloid-free solution. We conducted the experiment twice: first, with bees incubated under variable environmental conditions (‘Variable’; temperatures varied from 10-35°C with ambient lighting; and second, under carefully controlled environmental conditions (‘Stable’; 27°C incubator, constant darkness. In ‘Variable’, each alkaloid alone significantly decreased parasite loads, but this effect was not realized with the alkaloids in combination, suggesting an antagonistic interaction. Nicotine but not anabasine significantly increased mortality, and the two compounds had no interactive effects on mortality. In ‘Stable’, nicotine significantly increased parasite loads, the opposite of its effect in ‘Variable’. While not significant, the relationship between anabasine and parasite loads was also positive. Interactive effects between the two alkaloids on parasite load were non-significant, but the pattern of antagonistic interaction was similar to that in the variable experiment. Neither alkaloid, nor their interaction, significantly affected mortality under controlled conditions. Our results do not indicate synergy

  8. In vitro effects of nicotine on the non-small-cell lung cancer line A549.

    Science.gov (United States)

    Gao, Tao; Zhou, Xue-Liang; Liu, Sheng; Rao, Chang-Xiu; Shi, Wen; Liu, Ji-Chun

    2016-04-01

    To investigate in vitro effects of nicotine on the non-small-cell lung cancer line A549. The case-control study was conducted at the First Affiliated Hospital of Nanchang University from 1st January to 30th June, 2014 and comprised A549 cells which were treated with a series of concentrations of nicotine (0.01 µM, 0.1 µM, 1 µM and 10 µM) for 24 hours. Control cells were incubated under the same conditions without the addition of nicotine. Cell growth was detected by monotetrazolium salt [3-(4, 5-dimethyl-2-thiazolyl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. Cell apoptosis was detected by Haematoxylin and Eosin staining, immunofluorescence analysis of Filamentous actin and electron microscope observation. Nicotine had no significant effect on A549 cell growth at the dose of 0.01µM (p>0.05), but had significant growth inhibitory effects at the doses of 0.1µM, 1µM and 10µM (pA549 cells were found to be dose-dependent.

  9. Dual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans

    Science.gov (United States)

    Jasinska, Agnes J.; Zorick, Todd; Brody, Arthur L.; Stein, Elliot A.

    2013-01-01

    Substantial evidence demonstrates both nicotine’s addiction liability and its cognition-enhancing effects. However, the neurobiological mechanisms underlying nicotine’s impact on brain function and behavior remain incompletely understood. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation as well as for a number of cognitive disorders such as schizophrenia. Neuroimaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), which make it possible to study the actions of nicotine in the human brain in vivo, play an increasingly important role in identifying these dual mechanisms of action. In this review, we summarize the current state of knowledge and discuss outstanding questions and future directions in human neuroimaging research on nicotine and tobacco. This research spans from receptor-level PET and SPECT studies demonstrating nicotine occupancy at nicotinic acetylcholine receptors (nAChRs) and upregulation of nAChRs induced by chronic smoking; through nicotine’s interactions with the mesocorticolimbic dopamine system believed to mediate nicotine’s reinforcing effects leading to dependence; to functional activity and connectivity fMRI studies documenting nicotine’s complex behavioral and cognitive effects manifest by its actions on large-scale brain networks engaged both during task performance and at rest. PMID:23474015

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

    Science.gov (United States)

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

    2012-01-01

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

  11. Nicotine Vapor Inhalation Escalates Nicotine Self-Administration

    OpenAIRE

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

    2012-01-01

    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-hr operant sessions, then exposed to chronic intermittent (12 hrs/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hrs withdrawal. Rats were tested intermittently on days 1, 3 ...

  12. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    Science.gov (United States)

    Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

    2017-06-01

    Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

  13. Failure of hospital employees to comply with smoke-free policy is associated with nicotine dependence and motives for smoking: a descriptive cross-sectional study at a teaching hospital in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Turner Kenrick

    2009-07-01

    Full Text Available Abstract Background Smoke-free policy aims to protect the health of the population by reducing exposure to environmental tobacco smoke (ETS, and World Health Organisation (WHO guidance notes that these policies are only successful if there is full and proper enforcement. We aimed to investigate the problem of resistance to smoking restrictions and specifically compliance with smoke-free policy. We hypothesised that an explanation for non-compliance would lie in a measurable difference between the smoking behaviours of compliant and non-compliant smokers, specifically that non-compliance would be associated with nicotine dependence and different reasons for smoking. Methods We conducted a questionnaire-based, descriptive, cross-sectional study of hospital employees. Seven hundred and four members of staff at Addenbrooke's Hospital, Cambridge, UK, completed the questionnaire, of whom 101 were smokers. Comparison between compliant and non-compliant smokers was made based on calculated scores for the Fagerström test and the Horn-Waingrow scale, and level of agreement with questions about attitudes. For ordinal data we used a linear-by-linear association test. For non-parametric independent variables we used the Mann-Whitney test and for associations between categorical variables we used the chi-squared test. Results The demographic composition of respondents corresponded with the hospital's working population in gender, age, job profile and ethnicity. Sixty nine smokers reported they were compliant while 32 were non-compliant. Linear-by-linear association analysis of the compliant and non-compliant smokers' answers for the Fagerström test suggests association between compliance and nicotine dependence (p = 0.049. Mann-Whitney test analysis suggests there is a statistically significant difference between the reasons for smoking of the two groups: specifically that non-compliant smokers showed habitual smoking behaviour (p = 0.003. Overall

  14. Cellular Events in Nicotine Addiction

    OpenAIRE

    Penton, Rachel E.; Lester, Robin A.J.

    2009-01-01

    In the twenty-five years since the observation that chronic exposure to nicotine could regulate the number and function of high affinity nicotine binding sites in the brain there has been a major effort to link alterations in nicotinic acetylcholine receptors (nAChRs) to nicotine-induced behaviors that drive the addiction to tobacco products. Here we review the proposed roles of various nAChR subtypes in the addiction process, with emphasis on how they are regulated by nicotine and the implic...

  15. [(3)H]chlorpromazine photolabeling of the torpedo nicotinic acetylcholine receptor identifies two state-dependent binding sites in the ion channel.

    Science.gov (United States)

    Chiara, David C; Hamouda, Ayman K; Ziebell, Michael R; Mejia, Luis A; Garcia, Galo; Cohen, Jonathan B

    2009-10-27

    Chlorpromazine (CPZ), a potent nicotinic acetylcholine receptor (nAChR) noncompetitive antagonist, binds with higher affinity in the ion channel in the desensitized state than in the closed channel state and with low affinity to additional sites in nAChR-rich membranes. For nAChR equilibrated with agonist, we confirm previous reports that [(3)H]CPZ occupies a site near the cytoplasmic end of the M2 ion channel domain, photolabeling positions M2-2, M2-6, and/or M2-9 in each subunit. We find that [(3)H]CPZ also binds at the extracellular end of the channel, photolabeling amino acids at positions M2-16 (alpha,gamma), M2-17 (alpha,beta,delta), and M2-20 (alpha,beta,delta). The photolabeling at the cytoplasmic end of the channel is fully inhibitable by phencyclidine or proadifen, whereas neither drug inhibits [(3)H]CPZ photolabeling at the extracellular end, establishing that positively charged drugs can bind simultaneously at the cytoplasmic and extracellular ends of the ion channel. [(3)H]CPZ photolabeling is not detected in the transmembrane domain outside the ion channel, but it photolabels alphaMet-386 and alphaSer-393 in the cytoplasmic alphaMA helix. In the nAChR equilibrated with alpha-bungarotoxin to stabilize the nAChR in a closed state, [(3)H]CPZ photolabels amino acids at M2-5 (alpha), M2-6 (alpha,beta,delta), and M2-9 (beta,delta), with no labeling at M2-2. These results provide novel information about the modes of drug binding within the nAChR ion channel and indicate that within the nAChR transmembrane domain, the binding of cationic aromatic amine antagonists can be restricted to the ion channel domain, in contrast to the uncharged, allosteric potentiators and inhibitors that also bind within the delta subunit helix bundle and at subunit interfaces.

  16. Nicotine in high concentration causes contraction of isolated strips of rabbit corpus cavernosum.

    Science.gov (United States)

    Nguyen, Hoai Bac; Lee, Shin Young; Park, Soo Hyun; Han, Jun Hyun; Lee, Moo Yeol; Myung, Soon Chul

    2015-05-01

    It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

  17. Involvement of Hippocampal Jun-N Terminal Kinase Pathway in the Enhancement of Learning and Memory by Nicotine

    OpenAIRE

    Kenney, Justin W; Florian, Cédrick; Portugal, George S; Abel, Ted; Gould, Thomas J

    2009-01-01

    Despite intense scrutiny over the past 20 years, the reasons for the high addictive liability of nicotine and extreme rates of relapse in smokers have remained elusive. One factor that contributes to the development and maintenance of nicotine addiction is the ability of nicotine to produce long-lasting modifications of behavior, yet little is known about the mechanisms by which nicotine alters the underlying synaptic plasticity responsible for behavioral changes. This study is the first to e...

  18. Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT) Activity by Small Molecule GMX1778 Regulates Reactive Oxygen Species (ROS)-mediated Cytotoxicity in a p53- and Nicotinic Acid Phosphoribosyltransferase1 (NAPRT1)-dependent Manner*

    Science.gov (United States)

    Cerna, David; Li, Hongyun; Flaherty, Siobhan; Takebe, Naoko; Coleman, C. Norman; Yoo, Stephen S.

    2012-01-01

    Cancer cells undergo mitosis more frequently than normal cells and thus have increased metabolic needs, which in turn lead to higher than normal reactive oxygen species (ROS) production. Higher ROS production increases cancer cell dependence on ROS scavenging systems to balance the increased ROS. Selectively modulating intracellular ROS in cancers by exploiting cancer dependence on ROS scavenging systems provides a useful therapeutic approach. Essential to developing these therapeutic strategies is to maintain physiologically low ROS levels in normal tissues while inducing ROS in cancer cells. GMX1778 is a specific inhibitor of nicotinamide phosphoribosyltransferase, a rate-limiting enzyme required for the regeneration of NAD+ from nicotinamide. We show that GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD+ level. Notably, GMX1778 treatment does not induce ROS in normal cells. GMX1778-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner, but NAPRT1 is lost in a high frequency of glioblastomas, neuroblastomas, and sarcomas. In NAPRT1-deficient cancer cells, ROS induced by GMX1778 was not susceptible to treatment with NA. GMX1778-mediated ROS induction is p53-dependent, suggesting that the status of both p53 and NAPRT1 might affect tumor apoptosis, as determined by annexin-V staining. However, as determined by colony formation, GMX1778 long term cytotoxicity in cancer cells was only prevented by the addition of NA to NAPRT1-expressing cells. Exposure to GMX1778 may be a novel way of inducing ROS selectively in NAPRT1-negative tumors without inducing cytotoxic ROS in normal tissue. PMID:22570471

  19. Pathogenesis of Abdominal Aortic Aneurysms: Role of Nicotine and Nicotinic Acetylcholine Receptors

    Directory of Open Access Journals (Sweden)

    Zong-Zhuang Li

    2012-01-01

    Full Text Available Inflammation, proteolysis, smooth muscle cell apoptosis, and angiogenesis have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs, although the well-defined initiating mechanism is not fully understood. Matrix metalloproteinases (MMPs such as MMP-2 and -9 and other proteinases degrading elastin and extracellular matrix are the critical pathogenesis of AAAs. Among the risk factors of AAAs, cigarette smoking is an irrefutable one. Cigarette smoke is practically involved in various aspects of the AAA pathogenesis. Nicotine, a major alkaloid in tobacco leaves and a primary component in cigarette smoke, can stimulate the MMPs expression by vascular SMCs, endothelial cells, and inflammatory cells in vascular wall and induce angiogenesis in the aneurysmal tissues. However, for the inflammatory and apoptotic processes in the pathogenesis of AAAs, nicotine seems to be moving in just the opposite direction. Additionally, the effects of nicotine are probably dose dependent or associated with the exposure duration and may be partly exerted by its receptors—nicotinic acetylcholine receptors (nAChRs. In this paper, we will mainly discuss the pathogenesis of AAAs involving inflammation, proteolysis, smooth muscle cell apoptosis and angiogenesis, and the roles of nicotine and nAChRs.

  20. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

    2009-07-01

    Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

  1. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

    International Nuclear Information System (INIS)

    Suarez, S.V.; Changeux, J.P.; Granon, S.; Amadon, A.; Giacomini, E.; Le Bihan, D.; Wiklund, A.

    2009-01-01

    Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity β2-containing nicotinic receptors (β2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the β2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and β2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, β2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via α7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on β2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

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

    Science.gov (United States)

    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. © 2013 International Society for Neurochemistry.

  3. Pathways and Networks-Based Analysis of Candidate Genes Associated with Nicotine Addiction

    OpenAIRE

    Liu, Meng; Fan, Rui; Liu, Xinhua; Cheng, Feng; Wang, Ju

    2015-01-01

    Nicotine is the addictive substance in tobacco and it has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unclear. Under such situation, a comprehensive analysis focusing on the overall functional characteristics of these genes, as well as how the...

  4. Nitric oxide in the nucleus accumbens is involved in retrieval of inhibitory avoidance memory by nicotine.

    Science.gov (United States)

    Zarrindast, Mohammad Reza; Piri, Morteza; Nasehi, Mohammad; Ebrahimi-Ghiri, Mohaddeseh

    2012-03-01

    In the present study, the possible effect of nitric oxide agents injected into the nucleus accumbens (NAc) in the presence or absence of nicotine on morphine state-dependent memory in adult male Wistar rats was investigated. As a model of memory, a step-through type inhibitory avoidance task was used. Post-training injection of morphine (4 and 6mg/kg) dose dependently induced the impairment of memory retention. Administration of morphine (4 and 6mg/kg) before retention induced state-dependent retrieval of the memory acquired under post-training morphine (6mg/kg) influence. Injection of nicotine before retention (0.25 and 0.5mg/kg) alone and nicotine (0.1, 0.25 and 0.5mg/kg) plus an ineffective dose of morphine (2mg/kg) reversed the post-training morphine-induced memory impairment. The amnesia elicited by morphine (6mg/kg) was also prevented by pre-retention intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, l-NAME (0.24μg/rat, intra-NAc). Interestingly, an ineffective dose of nicotine (0.1mg/kg) in combination with low doses of l-NAME (0.06 and 0.12μg/rat, intra-NAc) synergistically improved memory performance impaired by morphine given after training. It is important to note that intra-NAc administration of l-NAME before retention impaired memory retrieval by itself. In contrast, pre-retention administration of l-arginine, a nitric oxide (NO) precursor (0.25 and 0.5μg/rat, intra-NAc), which had no effect alone, prevented the nicotine reversal of morphine effect on memory. The results suggest a possible role for nitric oxide of nucleus accumbens in the improving effect of nicotine on the morphine-induced amnesia and morphine state-dependent memory. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture.

    Science.gov (United States)

    Hastrup, Sidsel Gaarn; Chen, Xinqian; Bechtold, Joan E; Kyle, Richard F; Rahbek, Ole; Keyler, Daniel E; Skoett, Martin; Soeballe, Kjeld

    2010-09-01

    We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco (p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control (p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control (p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Use of Nicotine in Electronic Nicotine and Non-Nicotine Delivery Systems by US Adults, 2015.

    Science.gov (United States)

    Weaver, Scott R; Kemp, Catherine B; Heath, J Wesley; Pechacek, Terry F; Eriksen, Michael P

    Nicotine in electronic nicotine and non-nicotine delivery systems (ENDS/ENNDS) may present a risk of harm to those with cardiovascular disease and the fetuses of pregnant women. We assessed the extent to which adult users of ENDS/ENNDS used these products with nicotine. We obtained data for this study from a national probability survey of 6051 US adults that was conducted in August and September 2015. Of 399 adult ENDS/ENNDS users who were current smokers, 337 (80.7%) used ENDS/ENNDS containing nicotine, whereas only 29 of 71 (36.9%) ENDS/ENNDS users who were never smokers used ENDS/ENNDS containing nicotine. Assessments of the population health impact of ENDS/ENNDS use among never smokers should take into account the extent to which use involves nicotine.

  7. Nicotine inhibits potassium currents in Aplysia bag cell neurons

    Science.gov (United States)

    White, Sean H.; Sturgeon, Raymond M.

    2016-01-01

    Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

  8. Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls.

    Science.gov (United States)

    Tidey, Jennifer W; Cassidy, Rachel N; Miller, Mollie E

    2016-09-01

    Reducing the nicotine content of cigarettes to a minimally addictive level has been proposed as a regulatory strategy for reducing tobacco dependence. However, smokers with schizophrenia (SS) may be prone to changing their smoking topography in efforts to compensate for the reduction in nicotine content. The aims of this study were to compare smoking topography characteristics of usual-brand and very low nicotine content (VLNC) cigarettes in SS and control smokers without psychiatric illness (CS), and to determine whether nicotine replacement reversed any changes in topography produced by VLNC cigarettes. Using a within-subjects, counter-balanced design, SS (n = 27) and CS (n = 23) smoked usual brand cigarettes, VLNC cigarettes while wearing placebo patches (VLNC + PLA), or VLNC cigarettes while wearing transdermal nicotine patches totaling 42mg (VLNC + NIC) during 5-hour ad libitum smoking sessions. Cigarettes were smoked through topography measurement devices. Across conditions, SS smoked more puffs per session and per cigarette, had higher cigarette volumes, and had shorter inter-puff intervals than CS (Ps topography of usual brand versus VLNC cigarettes, combined with placebo or transdermal nicotine patches, in SS and controls. Although some changes in topography were indicative of compensatory smoking, total puffs and total cigarette volume were reduced with VLNC cigarettes, indicating that acute VLNC cigarette use does not increase smoking in SS. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Effects of nicotine on zebrafish: A comparative response between a newly established gill cell line and whole gills.

    Science.gov (United States)

    Nathiga Nambi, K S; Abdul Majeed, S; Taju, G; Sivasubbu, Sridhar; Sarath Babu, V; Sahul Hameed, A S

    2017-05-01

    A novel cell line, Danio rerio gill (DrG), derived from the gill tissue of zebrafish, was established and characterized. The cells were able to grow at a wide range of temperatures from 25°C to 32°C in Leibovitz's L-15 medium. The DrG cell line consists of epithelial-like cells with a diameter of 18-22μm. The cell line was characterized by mitochondrial 12S rRNA gene. Acute toxicity tests were conducted on D. rerio by exposing them to nicotine for 96h under static conditions. In vitro cytotoxicity of nicotine was assessed in DrG cell line using multiple endpoints such as 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), Neutral Red assay, Alamar Blue assay and Coomassie Blue protein assay. Linear correlations between each in vitro cytotoxicity assay and the in vivo mortality data were highly significant. Nicotine induced intracellular reactive oxygen species generation in DrG cell line in a concentration dependent manner. DrG cell line and zebrafish exposed to nicotine significantly increased the elevation of lipid peroxidation (LPO) while depletion of reduced glutathione (GSH), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione S-transferase (GST) and glutathione peroxidise(GPx1a) was observed. In nicotine treated fish and cells a negative correlation between reduced glutathione and LPO was observed. In addition, the production of ROS and the resulting oxidative stress resulted in increased expression of apoptosis related genes p53 and cas3.Collectively, our result suggests that nicotine has the potential to induce reactive oxygen species (ROS) production, oxidative stress and apoptosis in DrG cell line and zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Evaluation of nicotine in tobacco-free-nicotine commercial products.

    Science.gov (United States)

    Hellinghausen, Garrett; Lee, Jauh T; Weatherly, Choyce A; Lopez, Diego A; Armstrong, Daniel W

    2017-06-01

    Recently, a variety of new tobacco-free-nicotine, TFN, products have been commercialized as e-liquids. Tobacco-derived nicotine contains predominantly (S)-(-)-nicotine, whereas TFN products may not. The TFN products are said to be cleaner, purer substances, devoid of toxic components that come from the tobacco extraction process. A variety of commercial tobacco and TFN products were analyzed to identify the presence and composition of each nicotine enantiomer. A rapid and effective enantiomeric separation of nicotine has been developed using a modified macrocyclic glycopeptide bonded to superficially porous particles. The enantiomeric assay can be completed in nicotine, which is present in much greater quantities in commercial TFN products compared to commercial tobacco-derived products. Such studies are required by the FDA for new enantiomeric pharmacological products. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors.

    Science.gov (United States)

    Hedrick, Tristan; Waters, Jack

    2015-04-01

    The neuromodulator acetylcholine (ACh) shapes neocortical function during sensory perception, motor control, arousal, attention, learning, and memory. Here we investigate the mechanisms by which ACh affects neocortical pyramidal neurons in adult mice. Stimulation of cholinergic axons activated muscarinic and nicotinic ACh receptors on pyramidal neurons in all cortical layers and in multiple cortical areas. Nicotinic receptor activation evoked short-latency, depolarizing postsynaptic potentials (PSPs) in many pyramidal neurons. Nicotinic receptor-mediated PSPs promoted spiking of pyramidal neurons. The duration of the increase in spiking was membrane potential dependent, with nicotinic receptor activation triggering persistent spiking lasting many seconds in neurons close to threshold. Persistent spiking was blocked by intracellular BAPTA, indicating that nicotinic ACh receptor activation evoked persistent spiking via a long-lasting calcium-activated depolarizing current. We compared nicotinic PSPs in primary motor cortex (M1), prefrontal cortex (PFC), and visual cortex. The laminar pattern of nicotinic excitation was not uniform but was broadly similar across areas, with stronger modulation in deep than superficial layers. Superimposed on this broad pattern were local differences, with nicotinic PSPs being particularly large and common in layer 5 of M1 but not layer 5 of PFC or primary visual cortex (V1). Hence, in addition to modulating the excitability of pyramidal neurons in all layers via muscarinic receptors, synaptically released ACh preferentially increases the activity of deep-layer neocortical pyramidal neurons via nicotinic receptors, thereby adding laminar selectivity to the widespread enhancement of excitability mediated by muscarinic ACh receptors. Copyright © 2015 the American Physiological Society.

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

    Science.gov (United States)

    Donnerer, Josef; Liebmann, Ingrid

    2015-01-01

    In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability. © 2015 S. Karger AG, Basel.

  13. Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus.

    Science.gov (United States)

    Cohen, Ami; Soleiman, Matthew T; Talia, Reneta; Koob, George F; George, Olivier; Mandyam, Chitra D

    2015-01-01

    Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine dependence such as motivational withdrawal and increased motivation for nicotine after deprivation. The present study used extended access nicotine self-administration (0.03 mg/kg/infusion, 21 h/day, 4 days) with intermittent periods of deprivation (3 days) for 14 weeks, to test the hypothesis that this model enhances nicotine seeking and produces distinct responses in hippocampal neurogenesis when compared with limited access (1 h/day, 4 days) intake. Animals in the extended access group were either perfused prior to or following their final deprivation period, whereas animals in the limited access group were perfused after their last session. Limited- and extended access nicotine self-administration with periodic deprivation did not affect proliferation and differentiation of oligodendrocyte progenitors in the medial prefrontal cortex (mPFC). Conversely, extended access nicotine self-administration with periodic deprivation enhanced proliferation and differentiation of hippocampal neural progenitors. Furthermore, in the hippocampus, the number of differentiating NeuroD-labeled cells strongly and positively correlated with enhanced nicotine seeking in rats that experienced extended access nicotine self-administration. These findings demonstrate that extended versus limited access to nicotine self-administration differentially affects the generation of new oligodendroglia and new neurons during adulthood. The increases in the number of differentiating cells in extended access nicotine self-administering rats may consequently contribute to aberrant hippocampal neurogenesis and may contribute to maladaptive addiction-like behaviors dependent on the hippocampus.

  14. Self-Administered Nicotine Suppresses Body Weight Gain Independent of Food Intake in Male Rats.

    Science.gov (United States)

    Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C; Sved, Alan F

    2016-09-01

    The action of nicotine to suppress body weight is often cited as a factor impacting smoking initiation and the failure to quit. Despite the weight-suppressant effects of nicotine, smokers and nonsmokers report equal daily caloric intake. The weight-suppressive effects of nicotine in animal models of smoking are poorly understood. Furthermore, the Food and Drug Administration has authority to implement a policy markedly reducing nicotine levels in cigarettes; such a reduction could reduce smoking behavior, but have detrimental effects on body weight. The aim of this investigation was to examine the effects of self-administered nicotine on body weight and food intake in rats. In Experiment 1, rats with ad libitum access to chow responded for intravenous infusions of nicotine (60 µg/kg/infusion) or saline in daily 1-hour sessions; body weight and 24-hour food intake were measured. Experiment 2 tested the effects of subcutaneous injections of nicotine on food intake. In Experiment 3, rats were food restricted and self-administered nicotine across a range of doses (3.75-60 µg/kg/infusion) while body weight was measured. In Experiment 4, rats self-administered 60 µg/kg/infusion nicotine before reduction to one of several doses (1.875-15 µg/kg/infusion) for 50 days. Self-administered nicotine suppressed weight gain independent of food intake. In food restricted rats, self-administered nicotine dose-dependently suppressed body weight gain. In rats self-administering 60 µg/kg/infusion nicotine, dose reduction increased body weight. Self-administered nicotine, even at low doses, suppressed body independent of food intake; this may have important implications for nicotine reduction policy. The results of the present studies demonstrate that self-administered nicotine suppresses body weight independent of food intake in rats. Further, the present studies establish that self-administered nicotine suppresses body weight even at very low doses and that reduction of nicotine

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

    Science.gov (United States)

    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

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

    OpenAIRE

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

    2006-01-01

    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...

  17. Nicotine and periodontal tissues

    Directory of Open Access Journals (Sweden)

    Malhotra Ranjan

    2010-01-01

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

  18. GLP-1 acts on habenular avoidance circuits to control nicotine intake.

    Science.gov (United States)

    Tuesta, Luis M; Chen, Zuxin; Duncan, Alexander; Fowler, Christie D; Ishikawa, Masago; Lee, Brian R; Liu, Xin-An; Lu, Qun; Cameron, Michael; Hayes, Matthew R; Kamenecka, Theodore M; Pletcher, Matthew; Kenny, Paul J

    2017-05-01

    Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.

  19. Chronic ethanol or nicotine treatment results in partial cross-tolerance between these agents.

    Science.gov (United States)

    Burch, J B; de Fiebre, C M; Marks, M J; Collins, A C

    1988-01-01

    Female DBA/2Ibg mice were treated chronically (21 days) with ethanol- or dextrin-containing liquid diets or infused chronically with nicotine (8 mg/kg/h) or saline for 10 days. The responses of these animals to challenge doses of ethanol (2.5 g/kg) or nicotine (1 or 2 mg/kg) were measured using a test battery consisting of respiration rate, acoustic startle response, Y-maze crosses and rears, heart rate and body temperature. Chronic ethanol-treated animals were tolerant to the effects elicited by a challenge dose of ethanol on four of the six measures and were cross-tolerant to nicotine's effects on the acoustic startle test. Chronic nicotine-treated animals were tolerant to nicotine's effects on five of the six measures and cross-tolerant to ethanol's effects on heart rate and body temperature. Thus, partial cross-tolerance between ethanol and nicotine exists. Chronic nicotine treatment resulted in significant increases in L-[3H]-nicotine binding in six of seven brain regions and in alpha-[125I]-bungarotoxin binding in three of seven brain regions. Chronic ethanol treatment failed to alter the binding of either ligand. Therefore, the cross-tolerance that develops between ethanol and nicotine is not totally dependent on alterations in the number of brain nicotinic receptors.

  20. Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.

    Directory of Open Access Journals (Sweden)

    Tian-Ying Xu

    Full Text Available This study was to investigate the effect of nicotine on insulin sensitivity and explore the underlying mechanisms. Treatment of Sprague-Dawley rats with nicotine (3 mg/kg/day for 6 weeks reduced 43% body weight gain and 65% blood insulin level, but had no effect on blood glucose level. Both insulin tolerance test and glucose tolerance test demonstrated that nicotine treatment enhanced insulin sensitivity. Pretreatment of rats with hexamethonium (20 mg/kg/day to antagonize peripheral nicotinic receptors except for α7 nicotinic acetylcholine receptor (α7-nAChR had no effect on the insulin sensitizing effect of nicotine. However, the insulin sensitizing effect but not the bodyweight reducing effect of nicotine was abrogated in α7-nAChR knockout mice. Further, chronic treatment with PNU-282987 (0.53 mg/kg/day, a selective α7-nAChR agonist, significantly enhanced insulin sensitivity without apparently modifying bodyweight not only in normal mice but also in AMP-activated kinase-α2 knockout mice, an animal model of insulin resistance with no sign of inflammation. Moreover, PNU-282987 treatment enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3 in skeletal muscle, adipose tissue and liver in normal mice. PNU-282987 treatment also increased glucose uptake by 25% in C2C12 myotubes and this effect was total abrogated by STAT3 inhibitor, S3I-201. All together, these findings demonstrated that nicotine enhanced insulin sensitivity in animals with or without insulin resistance, at least in part via stimulating α7-nAChR-STAT3 pathway independent of inflammation. Our results contribute not only to the understanding of the pharmacological effects of nicotine, but also to the identifying of new therapeutic targets against insulin resistance.

  1. A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

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    Peter Muelken

    Full Text Available Avoidance of the negative affective (emotional symptoms of nicotine withdrawal (e.g., anhedonia, anxiety contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS thresholds (anhedonia-like behavior. Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c. on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day. Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these

  2. A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

    Science.gov (United States)

    Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

    2015-01-01

    Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

  3. Evolution of male life histories and age-dependent sexual signals under female choice

    Directory of Open Access Journals (Sweden)

    Joel J. Adamson

    2013-12-01

    Full Text Available Sexual selection theory models evolution of sexual signals and preferences using simple life histories. However, life-history models predict that males benefit from increasing sexual investment approaching old age, producing age-dependent sexual traits. Age-dependent traits require time and energy to grow, and will not fully mature before individuals enter mating competition. Early evolutionary stages pose several problems for these traits. Age-dependent traits suffer from strong viability selection and gain little benefit from mate choice when rare. Few males will grow large traits, and they will rarely encounter choosy females. The evolutionary origins of age-dependent traits therefore remain unclear. I used numerical simulations to analyze evolution of preferences, condition (viability and traits in an age-structured population. Traits in the model depended on age and condition (“good genes” in a population with no genetic drift. I asked (1 if age-dependent indicator traits and their preferences can originate depending on the strength of selection and the size of the trait; (2 which mode of development (age-dependent versus age-independent eventually predominates when both modes occur in the population; and (3 if age-independent traits can invade a population with age-dependent traits. Age-dependent traits evolve under weaker selection and at smaller sizes than age-independent traits. This result held in isolation and when the types co-occur. Evolution of age-independent traits depends only on trait size, whereas evolution of age-dependent traits depends on both strength of selection and growth rate. Invasion of age-independence into populations with established traits followed a similar pattern with age-dependence predominating at small trait sizes. I suggest that reduced adult mortality facilitates sexual selection by favoring the evolution of age-dependent sexual signals under weak selection.

  4. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

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    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, suc...

  5. Self-Administered Nicotine Suppresses Body Weight Gain Independent of Food Intake in Male Rats

    Science.gov (United States)

    Rupprecht, Laura E.; Smith, Tracy T.; Donny, Eric C.

    2016-01-01

    Introduction: The action of nicotine to suppress body weight is often cited as a factor impacting smoking initiation and the failure to quit. Despite the weight-suppressant effects of nicotine, smokers and nonsmokers report equal daily caloric intake. The weight-suppressive effects of nicotine in animal models of smoking are poorly understood. Furthermore, the Food and Drug Administration has authority to implement a policy markedly reducing nicotine levels in cigarettes; such a reduction could reduce smoking behavior, but have detrimental effects on body weight. The aim of this investigation was to examine the effects of self-administered nicotine on body weight and food intake in rats. Methods: In Experiment 1, rats with ad libitum access to chow responded for intravenous infusions of nicotine (60 µg/kg/infusion) or saline in daily 1-hour sessions; body weight and 24-hour food intake were measured. Experiment 2 tested the effects of subcutaneous injections of nicotine on food intake. In Experiment 3, rats were food restricted and self-administered nicotine across a range of doses (3.75–60 µg/kg/infusion) while body weight was measured. In Experiment 4, rats self-administered 60 µg/kg/infusion nicotine before reduction to one of several doses (1.875–15 µg/kg/infusion) for 50 days. Results: Self-administered nicotine suppressed weight gain independent of food intake. In food restricted rats, self-administered nicotine dose-dependently suppressed body weight gain. In rats self-administering 60 µg/kg/infusion nicotine, dose reduction increased body weight. Conclusions: Self-administered nicotine, even at low doses, suppressed body independent of food intake; this may have important implications for nicotine reduction policy. Implications: The results of the present studies demonstrate that self-administered nicotine suppresses body weight independent of food intake in rats. Further, the present studies establish that self-administered nicotine suppresses

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-12

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

  7. Endogenous cannabinoid and opioid systems and their role in nicotine addiction.

    Science.gov (United States)

    Maldonado, Rafael; Berrendero, Fernando

    2010-04-01

    Nicotine addiction is a complex behavioural alteration, in which many neuronal pathways and neurotransmitters are involved. For a long time, dopamine has been considered one of the most important neurotransmitters in mediating the rewarding effects of nicotine. In addition, a great amount of research suggests that the endogenous cannabinoid and opioid systems play an overall modulatory effect on the reward circuitry and participate in the addictive properties of most of the prototypical drugs of abuse. This review focuses on recent behavioural and biochemical data involving these systems in the different processes that contribute to tobacco addiction. A possible role for the endogenous cannabinoid and opioid systems in the rewarding properties of nicotine as well as in the development of nicotine physical dependence and relapse to nicotine-seeking behaviour will be examined. According to preclinical studies, clinical trials suggest that the manipulation of these systems with cannabinoid or opioid antagonists could be a potential therapeutical strategy for treating nicotine addiction.

  8. A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

    Science.gov (United States)

    Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

    1994-02-28

    Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

  9. Nicotine facilitates nicotinic acetylcholine receptor targeting to mitochondria but makes them less susceptible to selective ligands.

    Science.gov (United States)

    Uspenska, Kateryna; Lykhmus, Olena; Gergalova, Galyna; Chernyshov, Volodymyr; Arias, Hugo R; Komisarenko, Sergiy; Skok, Maryna

    2017-08-24

    Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in mitochondria to regulate the internal pathway of apoptosis in ion channel-independent manner. However, the mechanisms of nAChR activation in mitochondria and targeting to mitochondria are still unknown. Nicotine has been shown to favor nAChR pentamer assembly, folding, and maturation on the way of biosynthesis. The idea of the present work was to determine whether nicotine affects the content, glycosylation, and function of mitochondrial nAChRs. Experiments were performed in isolated liver mitochondria from mice, that either consumed or not nicotine with the drinking water (200μL/L) for 7days. Mitochondria detergent lysates were studied by sandwich or lectin ELISA for the presence and carbohydrate composition of different nAChR subunits. Intact mitochondria were examined by flow cytometry for the binding of fluorescently labeled α-cobratoxin and were tested in functional assay of cytochrome c release under the effect of either Ca 2+ or wortmannin in the presence or absence of nAChR-selective ligands, including PNU-282987 (1nM), dihydro-β-erythroidine (DhβE, 1μM), PNU-120596 (0.3, 3, or 10μM) and desformylflustrabromine hydrochloride (dFBr, 0.001, 0.3, or 1μM). It was found that nicotine consumption increased the ratio of mitochondrial vs non-mitochondrial nAChRs in the liver, enhanced fucosylation of mitochondrial nAChRs, but prevented the binding of α-cobratoxin and the cytochrome c release-attenuating effects of nAChR-specific agonists, antagonists, or positive allosteric modulators. It is concluded that nicotine consumption in vivo favors nAChR glycosylation and trafficking to mitochondria but makes them less susceptible to the effects of specific ligands. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A influência da genética na dependência tabágica e o papel da farmacogenética no tratamento do tabagismo The influence of genetics on nicotine dependence and the role of pharmacogenetics in treating the smoking habit

    Directory of Open Access Journals (Sweden)

    José Miguel Chatkin

    2006-12-01

    Full Text Available Mesmo com os esforços intensivos para o controle do tabagismo nas últimas décadas, uma proporção substancial de pessoas inicia a fumar ou mantém-se fumando apesar do pleno conhecimento dos malefícios do hábito. Os estudos têm focado atualmente as bases genéticas da adição nicotínica. O tabagismo tem sido associado a vários polimorfismos genéticos, mas os fatores ambientais também devem ser enfatizados. Esta revisão apresenta alguns dos principais dados disponíveis dos estudos genéticos sobre o comportamento tabágico. Esta linha de pesquisa poderá, no futuro, ajudar os clínicos a individualizar o tipo, a dosagem e a duração do tratamento da dependência tabágica, conforme o genótipo de cada fumante, maximizando a eficácia do esquema proposto.Despite the considerable efforts made in the fight against smoking in the last decades, there are still substantial numbers of people who, in full knowledge of the health hazards, begin smoking or continue smoking. Recent studies have focused on the genetic bases of the nicotine addiction. Various genetic polymorphisms have been associated with smoking. However, environmental factors have also been shown to play a role. In this review, we present some of the principal data collected in genetic studies of smoking behavior. The results obtained through this line of research will eventually aid clinicians in individualizing the type, dosage and duration of treatment for patients with nicotine dependence in accordance with the genotype of each smoker, thereby maximizing the efficacy of the proposed treatment regimen.

  11. Análise da utilização do Questionário de Tolerância de Fagerström (QTF como instrumento de medida da dependência nicotínica Analysis of the use of the Fagerström Tolerance Questionnaire as an instrument to measure nicotine dependence

    Directory of Open Access Journals (Sweden)

    LUIS SUÁREZ HALTY

    2002-07-01

    Full Text Available Introdução: O Hospital Universitário é referência na cidade de Rio Grande, no Rio Grande do Sul, para pneumopatas crônicos, sendo importante a existência de um programa para cessação do fumo. Objetivos: Analisar a utilização do Questionário de Tolerância de Fagerström como instrumento de medida da magnitude da dependência nicotínica do paciente tabagista e obter subsídios para planejar a conduta terapêutica mais adequada. Material e método: Aplicação do Questionário de Tolerância de Fagerström em pacientes adultos fumantes regulares, dos setores de Clínica Médica e Pneumologia do Hospital Universitário e Santa Casa de Rio Grande durante o período de 12 meses. Foram preenchidos 301 questionários válidos, sendo 40,5% dos entrevistados do sexo feminino e 59,5% do masculino. A média de idade dos participantes foi de 48,6 anos. Conforme a pontuação obtida com o questionário, os pacientes foram classificados segundo sua dependência nicotínica em cinco graus: muito baixa, baixa, média, elevada e muito elevada. Resultados: 54,9% dos fumantes pertenciam ao Grupo de Elevada Dependência Nicotínica (³ 6 pontos. Foi encontrada associação entre elevada dependência nicotínica e consumo diário de cigarros ou tempo até o fumar o primeiro cigarro do dia (p Introduction: The University Hospital is reference in the city of Rio Grande, in the State of Rio Grande do Sul, Southeast part of Brazil, for chronic lung disease patients, with a major smoking cessation program. Aim: The purpose of this work was to analyze the utilization of Fagerström Tolerance Questionnaire to assess the nicotine dependence of smoking patients with reference to individualization of treatment. Material and Method: The authors used the Fagerström Tolerance Questionnaire (FTQ in daily smoking adult patients from the Medical Clinic and Chest Medicine Units of the University Hospital and Rio Grande Santa Casa Hospital, during the period of one year

  12. Knowledge about nicotine among HIV-positive smokers: Implications for tobacco regulatory science policy.

    Science.gov (United States)

    Pacek, Lauren R; Rass, Olga; Johnson, Matthew W

    2017-02-01

    The present paper describes the general knowledge of smoking and nicotine among a sample of current smokers living with HIV (n=271) who were recruited via Amazon Mechanical Turk. Descriptive statistics were used to report sociodemographic and smoking characteristics, as well as knowledge about smoking and nicotine. The sample was comprised of relatively light smokers, both in terms of cigarettes per day (M=8.1, SD=9.7) and dependence (67.5% had low dependence according to the Heaviness of Smoking Index). The majority of participants correctly identified smoking as being a potential cause of various smoking-related conditions and correctly identified constituents in cigarette smoke. However, a majority of participants also misattributed nicotine as being a potential cause of smoking-related illness. Accurate knowledge about nicotine was low. These misperceptions are of particular concern for vulnerable populations, such as persons living with HIV, who are disproportionately burdened by the prevalence of smoking and associated morbidities and mortality. These misperceptions could have unintended consequences in the wake of a potential nicotine reduction policy, such that reduced nicotine content products are perceived as safer than normal nicotine content products currently available for sale. Additionally, incorrect knowledge about nicotine has implications for the uptake and continued use of nicotine replacement therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Granular insular cortex inactivation as a novel therapeutic strategy for nicotine addiction.

    Science.gov (United States)

    Forget, Benoit; Pushparaj, Abhiram; Le Foll, Bernard

    2010-08-01

    Nicotine is the principal component of tobacco smoke, resulting in addiction, and recent evidence suggests that damage to the insular cortex (insula) disrupts tobacco addiction in human smokers. However, the effect of an inactivation of this structure in an animal model of nicotine addiction has yet to be evaluated. To study this question, we investigated the effects of reversible inactivation of the granular insula by local injection of a gamma-aminobutyric acid agonists mixture (baclofen/muscimol) on nicotine self-administration (SA) under fixed and progressive ratio and on reinstatement of nicotine seeking induced by nicotine priming or nicotine-associated cues in rats. We also evaluated the effects of granular insula inactivation on food SA and relapse as a control. The inactivation of the granular insula decreased nicotine SA under both fixed and progressive ratios without affecting the SA of food under the same schedules of reinforcement. This inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues or nicotine priming without modifying the reinstatement of food seeking. Our study indicates that the integrity of the granular insula is necessary for exhibiting motivation to take nicotine and to relapse to nicotine seeking but not for consuming food pellets or to relapse for food seeking. Indeed, it might be interesting to study the effect of methods that are able to modulate the activity of the insula--such as repetitive transcranial magnetic stimulation or deep brain stimulation--on tobacco addiction and relapse in humans. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Cigarette Nicotine Content as a Moderator of the Relationship Between Negative Affect and Smoking.

    Science.gov (United States)

    Robinson, Jason D; Kypriotakis, George; Karam-Hage, Maher; Green, Charles E; Hatsukami, Dorothy K; Cinciripini, Paul M; Donny, Eric C

    2017-09-01

    Research suggests a strong association between negative affect (NA) and smoking. However, little is known about the association between NA and smoking among individuals who switch to reduced-nicotine cigarettes. The goal of this study was to examine the extent to which cigarette nicotine content moderates the relationship between NA and smoking over time. Seven hundred and seventeen participants, 237 in the normal nicotine content (NNC; 15.8 mg/g and usual brand) cigarette group and 480 in the very low nicotine content (VLNC; 2.4 mg/g nicotine or less) cigarette group, participated in a randomized trial that examined the effects of cigarette nicotine content on smoking behavior over 6 weeks. We used parallel process latent growth curve modeling to estimate the relationship between changes in NA and changes in the numbers of cigarettes smoked per day (CPD), from baseline to 6 weeks, as a function of cigarette nicotine content. The relationship between NA and investigational CPD reduced over time for those in the VLNC group, but not for those in the NNC group. There was no significant relationship between change in PA and CPD over time for either cigarette group. Smoking VLNC cigarettes disrupts the relationship between smoking and negative affect, which may help reduce nicotine dependence. This study suggests that the association between NA and smoking behavior is reduced over time among those that smoked reduced-nicotine content cigarettes. This provides additional evidence that smoking reduced-nicotine content cigarettes may help reduce nicotine dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Tachyphylaxis and sensitization to nicotine-induced tachycardiac and pressor effects after nicotine infusions.

    Science.gov (United States)

    Cruz, S L; Vidrio, H

    1997-01-01

    This work examined the effects of nicotine on mean arterial pressure and heart rate in non-anesthetized spinal rats. Nicotine (200 mg/kg) was administered as a single bolus, as infusions lasting 7.5, 15 or 30 min, and as a post-infusion bolus. A nicotine bolus increased pressure and rate. These effects were less marked as the rate of infusion decreased. The infusions affected differentially the effects of a subsequent bolus. Thus, while tachycardia was decreased, the blood pressure rise was increased. An initial transient bradycardia was observed after bolus administration, but not during infusions; this effect was unchanged after post-infusion boluses. Pharmacological analysis indicated that tachycardia and bradycardia were predominantly due to ganglionic stimulation, while adrenal and sympathetic nerve catecholamine release played a major role in the pressor response. These results indicate that slow nicotine infusions do not induce tachyphylaxis for all of the cardiovascular effects of a subsequent bolus, and that development of acute tolerance appears to depend on the mechanism of action of the response.

  16. Toward a comprehensive long term nicotine policy.

    Science.gov (United States)

    Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

    2005-06-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

  17. Sex and HIV serostatus differences in decision making under risk among substance-dependent individuals.

    Science.gov (United States)

    Martin, Eileen; Gonzalez, Raul; Vassileva, Jasmin; Maki, Pauline M; Bechara, Antoine; Brand, Matthias

    2016-01-01

    HIV+ individuals with and without substance use disorders make significantly poorer decisions when information about the probability and magnitude of wins and losses is not available. We administered the Game of Dice Task, a measure of decision making under risk that provides this information explicitly, to 92 HIV+ and 134 HIV- substance-dependent men and women. HIV+ participants made significantly poorer decisions than HIV- participants, but this deficit appeared more prominent among HIV+ women. These data indicate that decision making under risk is impaired among HIV+ substance-dependent individuals (SDIs). Potential factors for the HIV+ women's relatively greater impairment are discussed.

  18. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

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    Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  19. Location-Dependent Query Processing Under Soft Real-Time Constraints

    Directory of Open Access Journals (Sweden)

    Zoubir Mammeri

    2009-01-01

    Full Text Available In recent years, mobile devices and applications achieved an increasing development. In database field, this development required methods to consider new query types like location-dependent queries (i.e. the query results depend on the query issuer location. Although several researches addressed problems related to location-dependent query processing, a few works considered timing requirements that may be associated with queries (i.e., the query results must be delivered to mobile clients on time. The main objective of this paper is to propose a solution for location-dependent query processing under soft real-time constraints. Hence, we propose methods to take into account client location-dependency and to maximize the percentage of queries respecting their deadlines. We validate our proposal by implementing a prototype based on Oracle DBMS. Performance evaluation results show that the proposed solution optimizes the percentage of queries meeting their deadlines and the communication cost.

  20. Short-term nicotine exposure induces long-lasting modulation of gustatory plasticity inCaenorhabditis elegans.

    Science.gov (United States)

    Urushihata, Takuya; Wakabayashi, Tokumitsu; Osato, Shoichi; Yamashita, Tetsuro; Matsuura, Tetsuya

    2016-12-01

    Nicotine administration induces many effects on animal behavior. In wild-type Caenorhabditis elegans , gustatory plasticity results in reduced chemotaxis toward NaCl of otherwise attractive concentrations after pre-exposure to 100 mM NaCl in the absence of food. However, acute nicotine administration during a 15 min pre-exposure period inhibits gustatory plasticity, whereas chronic nicotine administration during worm development facilitates the plasticity. To investigate the relationship between the duration of nicotine administration and its effects, we exposed worms to nicotine for various periods during development. The modulatory effect of nicotine on gustatory plasticity was gradually switched from inhibition to facilitation with increased duration of nicotine administration. Moreover, inhibition of plasticity was sustained after relatively short-term chronic administration, with effects lasting for 45 h after the removal of nicotine. Similar to the acute inhibitory effect after 15 min nicotine pre-exposure, the inhibitory effect after short-term chronic administration was dependent on the nicotinic acetylcholine receptor subunit genes lev-1 and unc-29, and genes involved in serotonin biosynthesis bas-1 and tph-1 . The impaired inhibition in bas-1 and tph-1 mutants was recovered by exogenous serotonin, demonstrating that serotonin plays an important role in the long-lasting inhibitory effects of short-term chronic nicotine exposure.

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

    Science.gov (United States)

    Yagi, Shintaro; Tanida, Mamoru; Satomi, Jun

    2015-05-27

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

  2. Influence of δ-Opioid Receptors in the Behavioral Effects of Nicotine

    Science.gov (United States)

    Berrendero, Fernando; Plaza-Zabala, Ainhoa; Galeote, Lola; Flores, África; Bura, S Andreea; Kieffer, Brigitte L; Maldonado, Rafael

    2012-01-01

    Multiple studies in animal models and humans suggest that the endogenous opioid system is an important neurobiological substrate for nicotine addictive properties. In this study, we evaluated the participation of δ-opioid receptors in different behavioral responses of nicotine by using δ-opioid receptor knockout mice. Acute nicotine administration induced hypolocomotion and antinociception in wild-type mice, which were similar in knockout animals. The development of tolerance to nicotine-induced antinociception was also similar in both genotypes. In agreement, the expression and functional activity of δ-opioid receptors were not modified in the different layers of the spinal cord and brain areas evaluated after chronic nicotine treatment. The somatic manifestation of the nicotine withdrawal syndrome precipitated by mecamylamine was also similar in wild-type and δ-opioid receptor knockout mice. In contrast, nicotine induced a conditioned place preference in wild-type animals that was abolished in knockout mice. Moreover, a lower percentage of acquisition of intravenous nicotine self-administration was observed in mice lacking δ-opioid receptors as well as in wild-type mice treated with the selective δ-opioid receptor antagonist naltrindole. Accordingly, in-vivo microdialysis studies revealed that the enhancement in dopamine extracellular levels induced by nicotine in the nucleus accumbens was reduced in mutant mice. In summary, the present results show that δ-opioid receptors are involved in the modulation of nicotine rewarding effects. However, this opioid receptor does not participate either in several acute effects of nicotine or in the development of tolerance and physical dependence induced by chronic nicotine administration. PMID:22669166

  3. Interoceptive conditioning with nicotine using extinction and re-extinction to assess stimulus similarity with bupropion

    Science.gov (United States)

    Charntikov, Sergios; deWit, Nicole R.; Bevins, Rick A

    2014-01-01

    Bupropion is an atypical antidepressant that increases long-term quit rates of tobacco smokers. A better understanding of the relation between nicotine and this first-line medication may provide insight into improving treatment. For all experiments, rats first had nicotine (0.4 mg base/kg) and saline session intermixed; intermittent access to sucrose only occurred on nicotine session. Nicotine in this protocol comes to differentially control “anticipatory” dipper entries. To more closely examine the overlap in the interoceptive stimulus effects of nicotine and bupropion, we assessed whether subsequent prolonged and repeated non-reinforced (extinction) sessions with the bupropion stimulus could weaken responding to nicotine (i.e., transfer of extinction). We also examined whether retraining the discrimination after initial extinction and then conducting extinction again (i.e., re-extinction) with bupropion would affect responding. We found that bupropion (20 and 30 mg/kg) fully substituted for the nicotine stimulus in repeated 20-min extinction sessions. The extent of substitution in extinction did not necessarily predict performance in the transfer test (e.g., nicotine responding unchanged after extinction with 20 mg/kg bupropion). Generalization of extinction back to nicotine was not seen with 20 mg/kg bupropion even after increasing the number of extinction session from 6 to 24. Finally, there was evidence that learning in the initial extinction phase was retained in the re-extinction phase for nicotine and bupropion. These findings indicate that learning involving the nicotine stimuli are complex and that assessment approach for stimulus similarity changes conclusions regarding substitution by bupropion. Further research will be needed to identify whether such differences may be related to different facets of nicotine dependence and/or its treatment. PMID:25080073

  4. Hedonic Predictors of Tobacco Dependence: A Puff Guide to Smoking Cessation

    Science.gov (United States)

    2015-04-07

    For example, Henningfield and Goldberg ( 17) used a self- administration paradigm of intravenous nicotine to explore self- administration based on...2006. The effects of smoking deprivation and nicotine administration on emotional reactivity. Nicotine Tab. Res. 8:379-92 10. Davis TC, Long SW...18 Fagerstrom Test of Nicotine Dependence

  5. Nicotinic Receptors in the Dorsal and Ventral Hippocampus Differentially Modulate Contextual Fear Conditioning

    Science.gov (United States)

    Kenney, Justin W.; Raybuck, Jonathan D.; Gould, Thomas J.

    2012-01-01

    Nicotine administration alters various forms of hippocampus-dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, whereas nicotine infused into the ventral hippocampus resulted in deficits. Nicotine infusions into the ventral hippocampus did not alter hippocampus-independent cued fear conditioning or time spent in the open arm of the elevated plus maze, a measure of anxiety, suggesting the effects are due to alterations in contextual learning and not other general processes. Finally, results from using direct infusions of MLA, a low-affinity α7 nicotinic acetylcholine receptor (nAChR) antagonist, in conjunction with systemic nicotine, provide evidence that α7-nAChRs in the ventral hippocampus mediate the detrimental effect of ventral hippocampal nicotine on contextual fear learning. These results suggest that with systemic nicotine administration, competition exists between the dorsal and ventral hippocampus for behavioral control over contextual learning. PMID:22271264

  6. Advances in nicotine research in Addiction Biology.

    Science.gov (United States)

    Bernardi, Rick E

    2015-09-01

    The aim of Addiction Biology is to advance our understanding of the action of drugs of abuse and addictive processes via the publication of high-impact clinical and pre-clinical findings resulting from behavioral, molecular, genetic, biochemical, neurobiological and pharmacological research. As of 2013, Addiction Biology is ranked number 1 in the category of Substance Abuse journals (SCI). Occasionally, Addiction Biology likes to highlight via review important findings focused on a particular topic and recently published in the journal. The current review summarizes a number of key publications from Addiction Biology that have contributed to the current knowledge of nicotine research, comprising a wide spectrum of approaches, both clinical and pre-clinical, at the cellular, molecular, systems and behavioral levels. A number of findings from human studies have identified, using imaging techniques, alterations in common brain circuits, as well as morphological and network activity changes, associated with tobacco use. Furthermore, both clinical and pre-clinical studies have characterized a number of mechanistic targets critical to understanding the effects of nicotine and tobacco addiction. Together, these findings will undoubtedly drive future studies examining the dramatic impact of tobacco use and the development of treatments to counter nicotine dependence. © 2015 Society for the Study of Addiction.

  7. Nicotine promotes cell proliferation via α7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

    International Nuclear Information System (INIS)

    Wong, Helen Pui Shan; Yu Le; Lam, Emily Kai Yee; Tai, Emily Kin Ki; Wu, William Ka Kei; Cho, Chi Hin

    2007-01-01

    Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a β 1 - and β 2 -selective antagonist, respectively, suggesting the role of β-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferation and adrenaline production. Expression of α7-nicotinic acetylcholine receptor (α7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an α7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and DβH expression as well as adrenaline production. Taken together, through the action on α7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and β-adrenergic activation. These data reveal the contributory role α7-nAChR and β-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer

  8. Increased hepatic nicotine elimination after phenobarbital induction in the conscious rat

    International Nuclear Information System (INIS)

    Foth, H.; Walther, U.I.; Kahl, G.F.

    1990-01-01

    Elimination parameters of [14C]nicotine in conscious rats receiving nicotine (0.3 mg/kg) either intravenously or orally were studied. The oral availability of unchanged nicotine, derived by comparison of the respective areas under the concentration vs time curves (AUC), was 89%, indicating low hepatic extraction ratios of about 10%. Pretreatment of rats with phenobarbital (PB) markedly increased hepatic first-pass extraction of nicotine. The oral availability of unchanged nicotine in plasma dropped to 1.4% of the corresponding values obtained from PB-treated rats receiving nicotine iv. After PB pretreatment, the clearance of iv nicotine was increased approximately twofold over controls, much less than the observed more than ninefold increase of hepatic first-pass extraction. It is assumed that extrahepatic metabolism contributed significantly to the rapid removal of nicotine from the plasma. The elimination of cotinine, originating from nicotine administered either po or iv, was significantly increased by PB pretreatment, as determined by the ratio of corresponding AUCs. The pattern of nicotine metabolites in urine also indicated an increase in the rate of cotinine metabolic turnover. The amount of norcotinine in the organic extract of urine paralleled PB microsomal enzyme induction. The ratio between urinary concentrations of the normetabolite and cotinine correlated strongly with the PB-induced state of rat liver. This may be a suitable indicator of PB-inducible hepatic cytochrome P450 isoenzyme(s). Since smoking habits in man are feedback-regulated by nicotine plasma concentrations, a similar increase of nicotine elimination by microsomal enzyme induction in man may be of relevance for tobacco consumption

  9. The Role of Nicotinic Acetylcholine Receptors in the Medial Prefrontal Cortex and Hippocampus in Trace Fear Conditioning

    OpenAIRE

    Raybuck, J. D.; Gould, T. J.

    2010-01-01

    Acute nicotine enhances multiple types of learning including trace fear conditioning but the underlying neural substrates of these effects are not well understood. Trace fear conditioning critically involves the medial prefrontal cortex and hippocampus, which both express nicotinic acetylcholine receptors (nAChRs). Therefore, nicotine could act in either or both areas to enhance trace fear conditioning. To identify the underlying neural areas and nAChR subtypes, we examined the effects of inf...

  10. Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

    Science.gov (United States)

    Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

    2017-04-01

    Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine

  11. History-dependent coupled growth of creep damage under variable stress conditions

    Science.gov (United States)

    Kawai, M.

    1998-08-01

    A multiaxial constitutive model is presented for the description of the history-dependent inelastic and damage behavior of polycrystalline metallic materials in the high-temperature range under variable loading conditions. A particular emphasis is placed on a new formulation for the history-dependent material degradation which is based on a coupling between hardening and damage. The total damage is given by the sum of damage components which have different history dependence. The associated continuum damage variables are defined through their evolution equations coupled with hardening parameters involved with a kinematic hardening model. The non-classical coupling between hardening and damage is incorporated into the modified kinematic hardening model which has. been developed for describing the complicated hardening and softening behavior under repeated stress changes. Numerical simulations for different material parameters show that the proposed damage-coupled constitutive model can predict an acceleration as well as a deceleration of creep damage growth due to stress variations.

  12. Nicotine Delivery and Vaping Behavior Duringad LibitumE-cigarette Access.

    Science.gov (United States)

    St Helen, Gideon; Ross, Kathryn C; Dempsey, Delia A; Havel, Christopher M; Jacob, Peyton; Benowitz, Neal L

    2016-10-01

    To characterize vaping behavior and nicotine intake during ad libitum e-cigarette access. Thirteen adult e-cigarette users had 90 minutes of videotaped ad libitum access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session. Average puff duration and interpuff interval were 3.5±1.4 seconds (±SD) and 118±141 seconds, respectively. 12% of puffs were unclustered puffs while 43%, 28%, and 17% were clustered in groups of 2-5, 6-10, and >10 puffs, respectively. On average, 4.0±3.3 mg of nicotine was inhaled; the maximum plasma nicotine concentration (C max ) was 12.8±8.5 ng/mL. Among the 8 tank users, number of puffs was positively correlated with amount of nicotine inhaled, C max , and area under the plasma nicotine concentration-time curve (AUC 0 → 90min ) while interpuff interval was negatively correlated with C max and AUC 0 → 90 . Vaping patterns differ from cigarette smoking. Plasma nicotine levels were consistent with intermittent dosing of nicotine from e-cigarettes compared to the more bolus dosing from cigarettes. Differences in delivery patterns and peak levels of nicotine achieved could influence the addictiveness of e-cigarettes compared to conventional cigarettes.

  13. Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

    International Nuclear Information System (INIS)

    Zarrelli, Armando; DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio; Isidori, Marina; Lavorgna, Margherita; Passananti, Monica; Previtera, Lucio

    2012-01-01

    Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive ‘smoking’. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and 1 H and 13 C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: ► Processes of chlorination in the treatment of raw water. ► STP chlorination of nicotine. ► Genotoxic evaluation of main degradation products of nicotine.

  14. Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

    Energy Technology Data Exchange (ETDEWEB)

    Zarrelli, Armando, E-mail: zarrelli@unina.it [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); Isidori, Marina; Lavorgna, Margherita [Department of Life Sciences, II University of Naples, Caserta (Italy); Passananti, Monica; Previtera, Lucio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy)

    2012-06-01

    Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive 'smoking'. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and {sup 1}H and {sup 13}C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: Black-Right-Pointing-Pointer Processes of chlorination in the treatment of raw water. Black-Right-Pointing-Pointer STP chlorination of nicotine. Black-Right-Pointing-Pointer Genotoxic evaluation of main degradation products of nicotine.

  15. Pharmacological treatments for tobacco dependence

    Directory of Open Access Journals (Sweden)

    K. O. Fagerström

    2008-12-01

    Full Text Available There are currently three licensed therapies for smoking cessation: nicotine replacement (NR, bupropion and varenicline. NR can be indicated for: 1 aid in abrupt cessation; 2 gradual reduction in order to quit smoking; 3 temporary abstinence; and 4 smoking reduction maintenance. A meta-analysis has found that the relative risk of abstinence for any form of NR relative to control was 1.6. It has been found that starting NR treatment 1–3 weeks before smoking cessation and combining NR products, usually patch and gum, increases efficacy. Recently some new nicotine administration forms, i.e. lozenge, mouth spray and a pouch, have been developed. They seem to have the potential to relieve cravings faster than the current high-dose gum, and also be more preferred. Varenicline is a selective partial agonist at the 4β2 nicotinic acetylcholine receptors (nAChR. It decreases cravings and alleviates the symptoms of withdrawal. It can also reduce the rewarding and reinforcing effects of nicotine. Trials have shown varenicline to have increased efficacy relative to bupropion. Varenicline has also been compared with NR (21 mg transdermal patch in one randomised study. Abstinence at the end of treatment at 12 weeks was significantly increased for varenicline (56% compared with for nicotine patch (43%. Some post-marketing reports have expressed concern about psychiatric adverse effects, such as aggression, depression and suicides. The European Medicines Agency and the Food and Drug Administration of the USA are monitoring reported side-effects, but so far no confirmed casual relationship between these adverse effects and varenicline has been established. Bupropion inhibits neuronal re-uptake of dopamine and norepinephrine and is an antagonist on the nAChR. Its efficacy, compared with placebo, has been proved in several meta-analyses. A recent study suggests that longer pre-cessation use of bupropion, e.g. for 4 weeks, can improve efficacy results. Under

  16. The comparative efficacy of first- versus second-generation electronic cigarettes in reducing symptoms of nicotine withdrawal.

    Science.gov (United States)

    Lechner, William V; Meier, Ellen; Wiener, Josh L; Grant, DeMond M; Gilmore, Jenna; Judah, Matt R; Mills, Adam C; Wagener, Theodore L

    2015-05-01

    Currently, electronic cigarettes (e-cigarettes) are studied as though they are a homogeneous category. However, there are several noteworthy differences in the products that fall under this name, including potential differences in the efficacy of these products as smoking cessation aids. The current study examined the comparative efficacy of first- and second-generation e-cigarettes in reducing nicotine withdrawal symptoms in a sample of current smokers with little or no experience of using e-cigarettes. Twenty-two mildly to moderately nicotine-dependent individuals were randomized to a cross-over design in which they used first- and second-generation e-cigarettes on separate days with assessment of withdrawal symptoms directly prior to and after product use. A community-based sample recruited in the Midwest region of the United States reported a mean age of 28.6 [standard deviation (SD) = 12.9]. The majority were male (56.5%), Caucasian (91.3%), reported smoking an average of 15.2 (SD = 9.6) tobacco cigarettes per day, and a mean baseline carbon monoxide (CO) level of 18.7 parts per million (p.p.m.). Symptoms of withdrawal from nicotine were measured via the Mood and Physical Symptoms Scale. Analysis of changes in withdrawal symptoms revealed a significant time × product interaction F(1, 21)  = 5.057, P = 0.036, n(2) P  = 0.202. Participants experienced a larger reduction in symptoms of nicotine withdrawal after using second-generation compared with first-generation e-cigarettes. Second-generation e-cigarettes seem to be more effective in reducing symptoms of nicotine withdrawal than do first-generation e-cigarettes. © 2015 Society for the Study of Addiction.

  17. Personality types and nicotine dependency among medical ...

    African Journals Online (AJOL)

    Internet Journal of Medical Update - EJOURNAL. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 8, No 2 (2013) >. Log in or Register to get access to full text downloads.

  18. Dopamine and serotonin genetic risk scores predicting substance and nicotine use in attention deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Groenman, Annabeth P.; Greven, Corina U.; van Donkelaar, Marjolein M. J.; Schellekens, Arnt; van Hulzen, Kimm J. E.; Rommelse, Nanda; Hartman, Catharina A.; Hoekstra, Pieter J.; Luman, Marjolein; Franke, Barbara; Faraone, Stephen V.; Oosterlaan, Jaap; Buitelaar, Jan K.

    Individuals with attention deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways

  19. Moderation of Nicotine Effects on Covert Orienting of Attention Tasks by Poor Placebo Performance and Cue Validity

    Science.gov (United States)

    Gilbert, David G.; Rzetelny, Adam; Rabinovich, Norka E.

    2016-01-01

    Introduction and Rationale Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. Method The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. Results Compared to a placebo patch, a 14 mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. Conclusions These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine’s effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement. PMID:27461547

  20. Activation of nicotinic ACh receptors with alpha4 subunits induces adenosine release at the rat carotid body.

    Science.gov (United States)

    Conde, Sílvia V; Monteiro, Emília C

    2006-04-01

    The effect of ACh on the release of adenosine was studied in rat whole carotid bodies, and the nicotinic ACh receptors involved in the stimulation of this release were characterized. ACh and nicotinic ACh receptor agonists, cytisine, DMPP and nicotine, caused a concentration-dependent increase in adenosine production during normoxia, with nicotine being more potent and efficient in stimulating adenosine release from rat CB than cytisine and DMPP. D-Tubocurarine, mecamylamine, DHbetaE and alpha-bungarotoxin, nicotinic ACh receptor antagonists, caused a concentration-dependent reduction in the release of adenosine evoked by hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that inhibit adenosine release was DHbetaE>mecamylamine>D-tubocurarine>alpha-bungarotoxin. The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHbetaE, a selective nicotinic receptor antagonist. The ecto-5'-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. Taken together, these data indicate that ACh induced the production of adenosine, mainly from extracellular ATP catabolism at the CB through a mechanism that involves the activation of nicotinic receptors with alpha4 and beta2 receptor subunits.

  1. An estimator of the survival function based on the semi-Markov model under dependent censorship.

    Science.gov (United States)

    Lee, Seung-Yeoun; Tsai, Wei-Yann

    2005-06-01

    Lee and Wolfe (Biometrics vol. 54 pp. 1176-1178, 1998) proposed the two-stage sampling design for testing the assumption of independent censoring, which involves further follow-up of a subset of lost-to-follow-up censored subjects. They also proposed an adjusted estimator for the survivor function for a proportional hazards model under the dependent censoring model. In this paper, a new estimator for the survivor function is proposed for the semi-Markov model under the dependent censorship on the basis of the two-stage sampling data. The consistency and the asymptotic distribution of the proposed estimator are derived. The estimation procedure is illustrated with an example of lung cancer clinical trial and simulation results are reported of the mean squared errors of estimators under a proportional hazards and two different nonproportional hazards models.

  2. Use of nicotine replacement therapy in young people entering custody in New South Wales, Australia.

    Science.gov (United States)

    Haysom, Leigh; Lawrence, Dianne; Mellish, Donna; Burns, Peter; Khale, Pariza; Arulampalam, Ariana; Stapylton, Catherine

    2017-07-01

    To describe the prevalence of nicotine dependence and acceptance of nicotine replacement therapy (NRT) in young people entering custody, where smoking is not allowed. Cross-sectional study in 2013. All New South Wales Juvenile Justice Centres. Incarcerated youth, aged 12-21 years. gender, age, ethnicity, cannabis use. rates of smoking, cannabis use, nicotine dependence, NRT acceptance. Data were collected from 252 Initial Reception Assessments (90.1% male, 56.3% Aboriginal, mean age 16.6 years ± 1.2 standard deviation). According to Fagerstrom screening, 207 (82.1%) young people smoked cigarettes immediately prior to their current incarceration, and of the smokers, 78 (38.4%) were nicotine dependent. Most young people (76.4%) were also daily cannabis users, with 85.6% of cigarette smokers also using cannabis daily. NRT (as 24-h nicotine patches prescribed for 2 weeks) was offered to 54 nicotine dependent and 7 non-dependent young people. Only 13 (21.3%) young people accepted NRT (all daily cannabis-using males), and only 2 young people completed the full prescription. Reasons for refusing or not completing NRT were a fear of 'weird dreams', sleeping issues or that it was no longer needed. Many young people entering custody are nicotine-dependent cigarette smokers and daily cannabis users, and are at high risk of nicotine withdrawal on abstinence. NRT as patch therapy has poor acceptance in this group, except in young men who are daily cannabis users. Screening for nicotine dependence in high-risk young people should include questions about cannabis use, and alternatives to patch therapy deserve further research. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  3. Nicotine Elicits Methamphetamine-Seeking in Rats Previously Administered Nicotine

    OpenAIRE

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

    2009-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, ...

  4. Behavioural and biochemical evidence for interactions between Δ9-tetrahydrocannabinol and nicotine

    Science.gov (United States)

    Valjent, Emmanuel; Mitchell, Jennifer M; Besson, Marie-Jo; Caboche, Jocelyne; Maldonado, Rafael

    2002-01-01

    Behavioural and pharmacological effects of Δ9-tetrahydrocannabinol (THC) and nicotine are well known. However, the possible interactions between these two drugs of abuse remain unclear in spite of the current association of cannabis and tobacco in humans. The present study was designed to analyse the consequences of nicotine administration on THC-induced acute behavioural and biochemical responses, tolerance and physical dependence. Nicotine strongly facilitated hypothermia, antinociception and hypolocomotion induced by the acute administration of THC. Furthermore, the co-administration of sub-threshold doses of THC and nicotine produced an anxiolytic-like response in the light–dark box and in the open-field test as well as a significant conditioned place preference. Animals co-treated with nicotine and THC displayed an attenuation in THC tolerance and an enhancement in the somatic expression of cannabinoid antagonist-precipitated THC withdrawal. THC and nicotine administration induced c-Fos expression in several brain structures. Co-administration of both compounds enhanced c-Fos expression in the shell of the nucleus accumbens, central and basolateral nucleus of the amygdala, dorso-lateral bed nucleus of the stria terminalis, cingular and piriform cortex, and paraventricular nucleus of the hypothalamus. These results clearly demonstrate the existence of a functional interaction between THC and nicotine. The facilitation of THC-induced acute pharmacological and biochemical responses, tolerance and physical dependence by nicotine could play an important role in the development of addictive processes. PMID:11815392

  5. The effects of acute nicotine on contextual safety discrimination.

    Science.gov (United States)

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. © The Author(s) 2014.

  6. How does the quality of a prediction depend on the magnitude of the events under study?

    Directory of Open Access Journals (Sweden)

    S. Hallerberg

    2008-04-01

    Full Text Available We investigate the predictability of extreme events in time series. The focus of this work is to understand, under which circumstances large events are better predictable than smaller events. Therefore we use a simple prediction algorithm based on precursory structures which are identified via the maximum likelihood principle. Using theses precursory structures we predict threshold crossings in autocorrelated processes of order one, which are either Gaussian, exponentially or Pareto distributed. The receiver operating characteristic curve is used as a measure for the quality of predictions we find that the dependence on the event magnitude is closely linked to the probability distribution function of the underlying stochastic process. We evaluate this dependence on the probability distribution function numerically and in the Gaussian case also analytically. Furthermore, we study predictions of threshold crossings in correlated data, i.e., velocity increments of a free jet flow. The velocity increments in the free jet flow are in dependence on the time scale either asymptotically Gaussian or asymptotically exponential distributed. If we assume that the optimal precursory structures are used to make the predictions, we find that large threshold crossings are for all different types of distributions better predictable. These results are in contrast to previous results, obtained for the prediction of large increments, which showed a strong dependence on the probability distribution function of the underlying process.

  7. Evolution of dominance under frequency-dependent intraspecific competition in an assortatively mating population.

    Science.gov (United States)

    Peischl, Stephan; Schneider, Kristan A

    2010-02-01

    We study the evolution of higher levels of dominance as a response to negative frequency-dependent selection. In contrast to previous studies, we focus on the effect of assortative mating on the evolution of dominance under frequency-dependent intraspecific competition. We analyze a two-locus two-allele model, in which the primary locus has a major effect on a quantitative trait that is under a mixture of frequency-independent stabilizing selection, density-dependent selection, and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The second (modifier) locus determines the degree of dominance at the trait level. Additionally, the population mates assortatively with respect to similarities in the ecological trait. Our analysis shows that the parameter region in which dominance can be established decreases if small levels of assortment are introduced. In addition, the degree of dominance that can be established also decreases. In contrast, if assortment is intermediate, sexual selection for extreme types can be established, which leads to evolution of higher levels of dominance than under random mating. For modifiers with large effects, intermediate levels of assortative mating are most favorable for the evolution of dominance. For large modifiers, the speed of fixation can even be higher for intermediate levels of assortative mating than for random mating.

  8. Inhibition of PaCaMKII-E isoform in the dorsal unpaired median neurosecretory cells of cockroach reduces nicotine- and clothianidin-induced currents.

    Science.gov (United States)

    List, Olivier; Calas-List, Delphine; Taillebois, Emiliane; Juchaux, Marjorie; Heuland, Emilie; Thany, Steeve H

    2014-08-01

    Cellular responses to Ca(2+) require intermediary proteins such as calcium/calmodulin-dependent protein kinase II (CaMKII), which transduces the signal into downstream effects. We recently demonstrated that the cockroach genome encodes five different CaMKII isoforms, and only PaCaMKII-E isoform is specifically expressed in the dorsal unpaired median neurosecretory cells. In the present study, using antisense oligonucleotides, we demonstrated that PaCaMKII-E isoform inhibition reduced nicotine-induced currents through α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptor subtypes. Specifically, PaCaMKII-E isoform is sufficient to repress nicotinic current amplitudes as a result of its depression by antisense oligonucleotides. Similar results were found using the neonicotinoid insecticide clothianidin, which acted as a full agonist of dorsal unpaired median neuron nicotinic acetylcholine receptors. Clothianidin current amplitudes are strongly reduced under bath application of PaCaMKII-E antisense oligonucleotides but no significant results are found with α-bungarotoxin co-applied, demonstrating that CaMKII-E isoform affects nicotine currents through α-bungarotoxin-sensitive and -insensitive receptor subtypes whereas clothianidin currents are reduced via α-bungarotoxin-insensitive receptors. In addition, we found that intracellular calcium increase induced by nicotine and clothianidin were reduced by PaCaMKII-E antisense oligonucleotides, demonstrating that intracellular calcium increase induced by nicotine and clothianidin are affected by PaCaMKII-E inhibition. Cellular responses to Ca(2+) require intermediary proteins such as calcium/calmodulin-dependent protein kinase II (CaMKII). We recently demonstrated that the cockroach genome encodes five different CaMKII isoforms and only PaCaMKII-E isoform was specifically expressed in the dorsal unpaired median neurosecretory cells. Here we show that specific inhibition of PaCaMKII-E isoform is

  9. A Systematic Analysis of Candidate Genes Associated with Nicotine Addiction.

    Science.gov (United States)

    Liu, Meng; Li, Xia; Fan, Rui; Liu, Xinhua; Wang, Ju

    2015-01-01

    Nicotine, as the major psychoactive component of tobacco, has broad physiological effects within the central nervous system, but our understanding of the molecular mechanism underlying its neuronal effects remains incomplete. In this study, we performed a systematic analysis on a set of nicotine addiction-related genes to explore their characteristics at network levels. We found that NAGenes tended to have a more moderate degree and weaker clustering coefficient and to be less central in the network compared to alcohol addiction-related genes or cancer genes. Further, clustering of these genes resulted in six clusters with themes in synaptic transmission, signal transduction, metabolic process, and apoptosis, which provided an intuitional view on the major molecular functions of the genes. Moreover, functional enrichment analysis revealed that neurodevelopment, neurotransmission activity, and metabolism related biological processes were involved in nicotine addiction. In summary, by analyzing the overall characteristics of the nicotine addiction related genes, this study provided valuable information for understanding the molecular mechanisms underlying nicotine addiction.

  10. Nicotine as a discriminative stimulus for ethanol use.

    Science.gov (United States)

    Ginsburg, Brett C; Levy, Simon A; Lamb, R J

    2018-01-01

    Abused drugs reinforce behavior; i.e., they increase the probability of the behavior preceding their administration. Abused drugs can also act as discriminative stimuli; i.e., they can set the occasion for responding reinforced by another event. Thus, one abused drug could come to set the occasion for the use of another and this functional relationship may play a role in polysubstance abuse, where common patterns of use could result in this relationship. Here we establish nicotine (0.4mg/kg, ip 5-min pre-session) as a discriminative stimulus for behavior reinforced by ethanol (0.1ml 8% w/v po, versus food) and determine the ability of nicotine (0.02-0.4mg/kg), varenicline (0.1-3.0mg/kg), and ethanol (250 and 500mg/kg) to control responding for ethanol. We compare these results to those from rats where nicotine signaled food was available (and ethanol was not). Nicotine came to function as a discriminative stimulus. Nicotine and varenicline produced dose-dependent increases in responding on the nicotine-appropriate lever while ethanol produced responding on the vehicle-appropriate lever. Whether this responding occurred on the lever that produced ethanol or food access depended on the training condition. These results demonstrate that a drug can come to set the occasion for use of another and suggest that this behavioral mechanism could play an important role in the maintenance of and recovery from polysubstance abuse, depending on the pattern of use. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Effects of chronic buproprion and nicotine administration on cell genesis and DNA fragmentation in adult rat dentate gyrus

    OpenAIRE

    Scerri, Charles;

    2006-01-01

    Previous experiments have shown that chronic subcutaneous administration of nicotine dose-dependently inhibits the acquisition and retention of a spatial task in the Morris water maze and reduces cell genesis in the dentate gyrus (DG) of adult rats.1 In the present study, the effects of nicotine and buproprion, an atypical antidepressant used in smoking cessation, on dentate gyrus cell genesis and DNA fragmentation were investigated. The results show that nicotine, chronically infused for 21 ...

  12. Effects of nicotine withdrawal on panic-like response to breath holding: a placebo-controlled, double-blind, crossover patch study.

    Science.gov (United States)

    Cosci, Fiammetta; Bertoli, Giuly; Abrams, Kenneth

    2013-12-01

    Cigarette smoking may increase the likelihood of developing panic disorder. Periods of nicotine withdrawal, in particular, may promote panic in individuals high in anxiety sensitivity. We examined the importance of nicotine withdrawal in the occurrence of smoking and panic. We utilized a placebo-controlled, double-blind, randomized, crossover design. Fifty smokers underwent a breath-holding (BH) challenge after the transdermal administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline as well as directly before and after the challenges. Nicotine abstinence induced a decrease in heart rate and systolic blood pressure (BP) before the BH procedure (heart rate: 78.80 ± 11.43 under nicotine, 70.88 ± 10.83 under placebo; systolic BP: 124.90 ± 11.34 under nicotine, 121.18 ± 13.44 under placebo) and shorter BH duration relative to the nicotine patch condition. Nicotine abstinence did not, though, increase fear reactivity to the challenge. The findings for heart rate and BP are consistent with the stimulant properties of nicotine. The reduced capacity to maintain apnea under placebo might be due to carbon dioxide (CO2 ) hypersensitivity during periods of nicotine abstinence. The negative findings regarding fear reactivity might be due to BH being a relatively weak anxiogen. Future researchers are encouraged to employ CO2 -inhalation procedures to study the relationship between nicotine withdrawal and panic. © 2013 Wiley Periodicals, Inc.

  13. Public opinion about FDA regulation of menthol and nicotine.

    Science.gov (United States)

    Bolcic-Jankovic, Dragana; Biener, Lois

    2015-12-01

    Regulations that reduce nicotine and eliminate menthol in cigarettes have been proposed to the US Food and Drug Administration (FDA) as product alterations that could reduce smoking prevalence in the USA. This study sought to assess the public response to either action. A mail survey of a representative sample of 1074 adults was conducted in two major metropolitan areas to determine the level of support for immediate, gradual or no reduction of menthol and nicotine in cigarettes. There was more support for reducing nicotine (79%) than for reducing or removing menthol (59.5%). Most smokers (59.2%; 95% CI 50.7 to 67.2) and 36% of non-smokers (95% CI 31.7 to 40.8) opposed eliminating menthol, but few smokers (23.8%) or non-smokers (20.3%) were opposed to reducing nicotine. Logistic regression showed no significant effect of smoking status on support for reductions in nicotine, but that smokers were significantly less supportive than non-smokers of FDA action on menthol (OR=0.32, 95% CI 0.21 to 0.49). A significant race by smoking status interaction showed that African-American smokers were more supportive of removing menthol than non-African-American smokers. The greater smoker support for reductions in nicotine than menthol could be due to inaccurate beliefs about the disease risk associated with the two substances (ie, a belief that nicotine is more harmful than menthol), or to greater awareness of the sensory role that menthol plays in smokers' satisfaction. In any case, if FDA goes ahead with regulations to remove menthol, it will be important to develop strategies to reduce smoker resistance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

    Directory of Open Access Journals (Sweden)

    Azita Chehri

    2014-02-01

    Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

  15. A programmable smoke delivery device for PET imaging with cigarettes containing 11C-nicotine.

    Science.gov (United States)

    Zuo, Yantao; Garg, Pradeep K; Nazih, Rachid; Garg, Sudha; Rose, Jed E; Murugesan, Thangaraju; Mukhin, Alexey G

    2017-05-01

    PET imaging with 11 C-nicotine-loaded cigarettes is a valuable tool to directly assess fast nicotine kinetics and its neuropharmacological role in tobacco dependence. To eliminate variations among puffs inhaled by subjects, this work aimed to develop a programmable smoke delivery device (SDD) to produce highly reproducible and adjustable puffs of cigarette smoke for PET experiments. The SDD was built around a programmable syringe pump as a smoking machine to draw a puff of smoke from a 11 C-nicotine-loaded cigarette and make it available for a subject to take the smoke into the mouth and then inhale it during PET data acquisition. Brain nicotine time activity curves and total body absorbed 11 C-nicotine doses (TAD) were measured in smokers who inhaled a single puff of smoke via the SDD from a 11 C-nicotine-loaded cigarette. Nearly identical brain nicotine kinetics were observed between participants who inhaled a puff of smoke through the SDD and those who inhaled directly from a cigarette. This new device minimizes puff variations that exist with earlier smoke delivery apparatuses which could introduce confounding factors. The SDD is effective in delivering 11 C-nicotine from the study cigarettes. Despite a 2-s increase in aging of smoke delivered through the SDD versus smoke taken directly from a cigarette, the difference in brain nicotine kinetics after 11 C-nicotine delivery with and without use of the SDD is negligible. This refined device may be useful for future research on the deposition and pharmacokinetics of nicotine inhaled with tobacco smoke. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Inventory Model for Deteriorating Items with Quadratic Time Dependent Demand under Trade Credits

    Directory of Open Access Journals (Sweden)

    Rakesh Tripathi

    2016-02-01

    Full Text Available In this paper, an EOQ model is developed for a deteriorating item with quadratic time dependent demand rate under trade credit. Mathematical models are also derived under two different situations i.e. Case I; the credit period is less than the cycle time for settling the account and Case II; the credit period is greater than or equal to the cycle time for settling the account. The numerical examples are also given to validate the proposed model. Sensitivity analysis is given to study the effect of various parameters on ordering policy and optimal total profit. Mathematica 7.1 software is used for finding optimal numerical solutions.

  17. Nitric oxide synthase inhibition ameliorates nicotine-induced sperm function decline in male rats

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    Ibukun P. Oyeyipo

    2015-09-01

    Conclusion: Taken together, the present data indicate the abilities of l-NAME to ameliorate nicotine-induced spermatotoxic effects in male rats via a mechanism dependent on the circulating testosterone level.

  18. Plane strain bending under tension as an ideal flow process in pressure – dependent plasticity

    Directory of Open Access Journals (Sweden)

    Alexandrov Sergei

    2017-01-01

    Full Text Available Ideal plastic flows are those for which all material elements follow minimum work paths. Ideal flow solutions are widely used as the basis for inverse methods for the preliminary design of metalworking processes. The present paper provides the first ideal flow solution in pressure-dependent plasticity. In particular, the process of bending under tension is considered and it is shown that there are relations between the bending moment and tensile force that result in ideal flow paths.

  19. On Critical Buckling Loads of Columns under End Load Dependent on Direction.

    Science.gov (United States)

    Başbük, Musa; Eryılmaz, Aytekin; Atay, M Tarık

    2014-01-01

    Most of the phenomena of various fields of applied sciences are nonlinear problems. Recently, various types of analytical approximate solution techniques were introduced and successfully applied to the nonlinear differential equations. One of the aforementioned techniques is the Homotopy analysis method (HAM). In this study, we applied HAM to find critical buckling load of a column under end load dependent on direction. We obtained the critical buckling loads and compared them with the exact analytic solutions in the literature.

  20. Characterization of nicotine binding in mouse brain and comparison with the binding of alpha-bungarotoxin and quinuclidinyl benzilate

    International Nuclear Information System (INIS)

    Marks, M.J.; Collins, A.C.

    1982-01-01

    The binding of [ 3 H]nicotine to mouse brain has been measured and subsequently compared with the binding of [ 125 I]alpha-bungarotoxin (alpha-BTX) and L-[ 3 H]quinuclidinyl benzilate (QNB). The binding of nicotine was saturable, reversible, and stereospecific. The average KD and Bmax were 59 nM and 88 fmoles/mg of protein, respectively. Although the rates of association and dissociation of nicotine were temperature-dependent, the incubation temperature had no effect on either KD or Bmax. When measured at 20 degrees or 37 degrees, nicotine appeared to bind to a single class of binding sites, but a second, very low-affinity, binding site was observed at 4 degrees. Nicotine binding was unaffected by the addition of NaCl, KCl, CaCl 2 , or MgSO 4 to the incubation medium. Nicotinic cholinergic agonists were potent inhibitors of nicotine binding; however, nicotinic antagonists were poor inhibitors. The regional distribution of binding was not uniform: midbrain and striatum contained the highest number of receptors, whereas cerebellum had the fewest. Differences in site densities, regional distribution, inhibitor potencies, and thermal denaturation indicated that nicotine binding was not the same as either QNB or alpha-BTX binding, and therefore that receptors for nicotine may represent a unique population of cholinergic receptors

  1. Bases neurofisiológicas da dependência do tabaco Neurophysiological basis of tobacco dependence

    Directory of Open Access Journals (Sweden)

    Cleopatra S. Planeta

    2005-10-01

    Full Text Available A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.It is generally accepted that nicotine is the major component in tobacco smoke responsible for addiction. Several studies have demonstrated that the neural mechanisms underlying nicotine addiction have much in common with those underlying the mechanisms of addiction to other drugs. Thus, it has been shown that nicotine induces conditioning place preference and self-administration across many species. Repeated treatment with nicotine also induces behavioral sensitization in

  2. Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice.

    Science.gov (United States)

    Balerio, Graciela N; Aso, Ester; Berrendero, Fernando; Murtra, Patricia; Maldonado, Rafael

    2004-11-01

    The possible interactions between Delta9-tetrahydrocannabinol (Delta9-THC) and nicotine remain unclear in spite of the current association of cannabis and tobacco in humans. The aim of the present study was to explore the interactions between these two drugs of abuse by evaluating the consequences of Delta9-THC administration on the somatic manifestations and the aversive motivational state associated with nicotine withdrawal in mice. Acute Delta9-THC administration significantly decreased the incidence of several nicotine withdrawal signs precipitated by mecamylamine or naloxone, such as wet-dog-shakes, paw tremor and scratches. In both experimental conditions, the global withdrawal score was also significantly attenuated by acute Delta9-THC administration. This effect of Delta9-THC was not due to possible adaptive changes induced by chronic nicotine on CB1 cannabinoid receptors, as the density and functional activity of these receptors were not modified by chronic nicotine administration in the different brain structures investigated. We also evaluated the consequences of Delta9-THC administration on c-Fos expression in several brain structures after chronic nicotine administration and withdrawal. c-Fos was decreased in the caudate putamen and the dentate gyrus after mecamylamine precipitated nicotine withdrawal. However, acute Delta9-THC administration did not modify c-Fos expression under these experimental conditions. Finally, Delta9-THC also reversed conditioned place aversion associated to naloxone precipitated nicotine withdrawal. Taken together, these results indicate that Delta9-THC administration attenuated somatic signs of nicotine withdrawal and this effect was not associated with compensatory changes on CB1 cannabinoid receptors during chronic nicotine administration. In addition, Delta9-THC also ameliorated the aversive motivational consequences of nicotine withdrawal.

  3. Biodegradation and metabolic pathway of nicotine in Rhodococcus sp. Y22.

    Science.gov (United States)

    Gong, Xiaowei; Ma, Guanghui; Duan, Yanqing; Zhu, Donglai; Chen, Yongkuan; Zhang, Ke-Qin; Yang, Jinkui

    2016-11-01

    Nicotine in tobacco is harmful to health and the environment, so there is an environmental requirement to remove nicotine from tobacco and tobacco wastes. In this study, the biotransformation of nicotine by Rhodococcus sp. Y22 was investigated, and three metabolites (NIC1, NIC4 and NIC5) were isolated by column separation, preparative TLC and solid plate's method, respectively. NIC1 was identified as 6-hydoxynicotine based on the results of NMR, MS, HPLC-UV and HRESIMS analysis; NIC4 was a novel compound and identified as 5-(3-methyl-[1,3]oxazinan-2-ylidene)-5H-pyridin-2-one based on the results of NMR, MS and UV analysis; NIC5 was identified as nicotine blue based on the results of NMR and MS analysis. Meanwhile, two metabolites NIC2 and NIC3 were identified as 6-hydroxy-N-methylmyosmine and 6-hydroxypseudooxynicotine by HRESIMS analysis, respectively. According to these metabolites, the possible pathway of nicotine degradation by Rhodococcus sp. Y22 was proposed. The nicotine can be transformed to nicotine blue through two pathways (A and B), and 6-hydroxy-N-methylmyosmine is the key compound, which can be converted to 6-hydroxypseudooxynicotine (pathway A) and 5-(3-methyl-[1,3]oxazinan-2-ylidene)-5H-pyridin-2-one (pathway B), respectively. Moreover, the encoding gene of nicotine dehydrogenase, ndh, was amplified from Rhodococcus sp. Y22, and its transcriptional level could be up-regulated obviously under nicotine induction. Our studies reported the key metabolites and possible biotransformation pathway of nicotine in Rhodococcus sp. Y22, and provided new insights into the microbial metabolism of nicotine.

  4. Nicotine stimulates expression of proteins implicated in peripheral and central sensitization.

    Science.gov (United States)

    Hawkins, J L; Denson, J E; Miley, D R; Durham, P L

    2015-04-02

    Pain patients who are nicotine dependent report a significantly increased incidence and severity of pain intensity. The goal of this study was to determine the effects of prolonged nicotine administration on inflammatory proteins implicated in the development of peripheral and central sensitization of the trigeminal system. Behavioral, immunohistochemical, and microarray studies were utilized to investigate the effects of nicotine administered daily for 14 days via an Alzet® osmotic pump in Sprague Dawley rats. Systemic nicotine administration caused a significant increase in nocifensive withdrawals to mechanical stimulation of trigeminal neurons. Nicotine stimulated expression of the pro-inflammatory signal transduction proteins phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-c-Jun N-terminal kinase (p-JNK), and protein kinase A (PKA) in the spinal trigeminal nucleus. Nicotine also promoted elevations in the expression of glial fibrillary acidic protein (GFAP), a biomarker of activated astrocytes, and the microglia biomarker ionized calcium-binding adapter molecule 1 (Iba1). Similarly, levels of eleven cytokines were significantly elevated with the largest increase in expression of TNF-α. Levels of PKA, p-ERK, and p-JNK in trigeminal ganglion neurons were increased by nicotine. Our findings demonstrate that prolonged systemic administration of nicotine promotes sustained behavioral and cellular changes in the expression of key proteins in the spinal trigeminal nucleus and trigeminal ganglion implicated in the development and maintenance of peripheral and central sensitization. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine

    Directory of Open Access Journals (Sweden)

    Ilya Sukhanov

    2018-04-01

    Full Text Available Trace amine-associated receptor 1 (TAAR1 has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg. The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted.

  6. Antibacterial activity of nicotine and its copper complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Cu(II)-nicotine was isolated from leaves of Nicotiana tabacum using metal ions following the method of Munir et al., 1994. Their antibacterial activity against ten different species of gram positive and gram negative bacteria were studied. For comparative study, pure sample of nicotine and metal salts used for complexation; Copper(II) chloride were also subjected to antibacterial tests with the same species of bacteria under similar conditions. Results indicated that nicotine had no effect on all the bacteria tested except Escherichia coli, Pseudomonas aeroginosa and Enterococcus faecalis, which showed 14 mm zone of inhibition at 200 mu g l00 mul/sup -1/ Copper(II) chloride was found to be effective against seven species and ineffective against three species of selected bacteria. On the other hand, Cu(II)-nicotine complex was ineffective against five species of bacteria at lower level while at higher level, only one species of bacteria showed resistance against this complex. The complex was compared with three standard antibiotics. Thus, this complex can be used against a variety of microorganisms at higher level. (author)

  7. The 5-HT2C Receptor Agonist Lorcaserin Reduces Nicotine Self-Administration, Discrimination, and Reinstatement: Relationship to Feeding Behavior and Impulse Control

    Science.gov (United States)

    Higgins, Guy A; Silenieks, Leo B; Roßmann, Anne; Rizos, Zoe; Noble, Kevin; Soko, Ashlie D; Fletcher, Paul J

    2012-01-01

    Lorcaserin ((1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl) is a selective 5-HT2C receptor agonist with clinical efficacy in phase-III obesity trials. Based on evidence that this drug class also affects behaviors motivated by drug reinforcement, we compared the effect of lorcaserin on behavior maintained by food and nicotine reinforcement, as well as the stimulant and discriminative stimulus properties of nicotine in the rat. Acutely administered lorcaserin (0.3–3 mg/kg, subcutaneous (SC)) dose dependently reduced feeding induced by 22-h food deprivation or palatability. Effects up to 1 mg/kg were consistent with a specific effect on feeding motivation. Lorcaserin (0.6–1 mg/kg, SC) reduced operant responding for food on progressive and fixed ratio schedules of reinforcement. In this dose range lorcaserin also reversed the motor stimulant effect of nicotine, reduced intravenous self-administration of nicotine, and attenuated the nicotine cue in rats trained to discriminate nicotine from saline. Lorcaserin also reduced the reinstatement of nicotine-seeking behavior elicited by a compound cue comprising a nicotine prime and conditioned stimulus previously paired with nicotine reinforcement. Lorcaserin did not reinstate nicotine-seeking behavior or substitute for a nicotine cue. Finally, lorcaserin (0.3–1 mg/kg) reduced nicotine-induced increases in anticipatory responding, a measure of impulsive action, in rats performing the five-choice serial reaction time task. Importantly, these results indicate that lorcaserin, and likely other selective 5-HT2C receptor agonists, similarly affect both food- and nicotine-motivated behaviors, and nicotine-induced impulsivity. Collectively, these findings highlight a therapeutic potential for 5-HT2C agonists such as lorcaserin beyond obesity into addictive behaviors, such as nicotine dependence. PMID:22189292

  8. Time-dependent scattering of incident light of various wavelengths in ferrofluids under external magnetic field

    Science.gov (United States)

    Jin, Jingyu; Song, Dongxing; Geng, Jiafeng; Jing, Dengwei

    2018-02-01

    Ferrofluids can exhibit the anisotropic thermodynamic properties under magnetic fields. The dynamic optical properties of ferrofluids in the presence of magnetic fields are of particular interest due to their potential application as various optical devices. Although time-dependent light scattering by ferrofluids have been extensively studied, the effect of wavelength of incident light have been rarely considered. Here, for the first time, we investigated both the time- and wavelength-dependent light scattering in water based ferrofluids containing Fe3O4 nanoparticles under an external magnetic field. The field-induced response behavior of the prepared ferrofluid samples was determined and verified first by thermal conductivity measurement and numerical simulation. Double-beam UV-Vis spectrophotometer was employed to record the temporal evolution of transmitted intensity of incident light of various wavelengths passing through the ferrofluid sample and propagating parallel to the applied field. As expected, the light intensity decreases to a certain value right after the field is turned on due to the thermal fluctuation induced disorder inside the flexible particle chains. Then the light intensity further decreases with time until the appearance of a minimum at time τ0 followed by an inversed increase before finally reaches equilibrium at a particular time. More importantly, the characteristic inversion time τ0 was found to follow a power law increase with the wavelength of incident light (τ0 ∼ λα, where α = 2.07). A quantitative explanation for the wavelength dependence of characteristic time was proposed based on the finite-difference time-domain (FDTD) method. The simulation results are in good agreement with our experimental observations. The time-dependent light scattering in ferrofluids under different incident wavelengths was rationalized by considering both the coarsening process of the particle chains and the occurrence of resonance within the

  9. Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

    Science.gov (United States)

    Brossard, Patrick; Weitkunat, Rolf; Poux, Valerie; Lama, Nicola; Haziza, Christelle; Picavet, Patrick; Baker, Gizelle; Lüdicke, Frank

    2017-10-01

    Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use. Maximal nicotine concentration (C max ) and area under the curve from start of product use to time of last quantifiable concentration (AUC 0-last ) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for C max and from 96 to 98% for AUC 0-last . Urge-to-smoke total scores were comparable between THS and CC. The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Nicotine Withdrawal; Measure Your Symptoms (Quiz)

    Science.gov (United States)

    ... Free Resources Medications Can Help You Quit Using Nicotine Replacement Therapy Busting NRT Myths Smokefree Phone Apps ... Withdrawal Understanding Withdrawal Quiz: How Strong is Your Nicotine Addiction? Quiz: What Are Your Withdrawal Symptoms? Dealing ...

  11. Electronic Nicotine Delivery Systems Key Facts Infographic

    Data.gov (United States)

    U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

  12. Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study.

    Directory of Open Access Journals (Sweden)

    Jasmin H Bavarva

    Full Text Available Nicotine is a known risk factor for cancer development and has been shown to alter gene expression in cells and tissue upon exposure. We used Illumina® Next Generation Sequencing (NGS technology to gain unbiased biological insight into the transcriptome of normal epithelial cells (MCF-10A to nicotine exposure. We generated expression data from 54,699 transcripts using triplicates of control and nicotine stressed cells. As a result, we identified 138 differentially expressed transcripts, including 39 uncharacterized genes. Additionally, 173 transcripts that are primarily associated with DNA replication, recombination, and repair showed evidence for alternative splicing. We discovered the greatest nicotine stress response by HPCAL4 (up-regulated by 4.71 fold and NPAS3 (down-regulated by -2.73 fold; both are genes that have not been previously implicated in nicotine exposure but are linked to cancer. We also discovered significant down-regulation (-2.3 fold and alternative splicing of NEAT1 (lncRNA that may have an important, yet undiscovered regulatory role. Gene ontology analysis revealed nicotine exposure influenced genes involved in cellular and metabolic processes. This study reveals previously unknown consequences of nicotine stress on the transcriptome of normal breast epithelial cells and provides insight into the underlying biological influence of nicotine on normal cells, marking the foundation for future studies.

  13. Nicotinic actions on neuronal networks for cognition: general principles and long-term consequences.

    Science.gov (United States)

    Poorthuis, Rogier B; Goriounova, Natalia A; Couey, Jonathan J; Mansvelder, Huibert D

    2009-10-01

    Nicotine enhances cognitive performance in humans and laboratory animals. The immediate positive actions of nicotine on learning, memory and attention are well-documented. Several brain areas involved in cognition, such as the prefrontal cortex, have been implicated. Besides acute effects on these brain areas and on brain function, a picture is emerging showing that long-term consequences of nicotine exposure during adolescence can be detrimental for cognitive performance. The majority of adult smokers started the habit during adolescence. Our knowledge on the types of nicotinic receptors in the brain areas that are candidates for mediating nicotine's effects is increasing. However, much less is known about the underlying cellular mechanisms. A series of recent studies have uncovered exciting features of the mechanisms by which nicotine alters prefrontal cortex neuronal activity, synaptic plasticity, gene expression and cognitive function, and how these changes may have a lasting effect on the developing brain. In this review, we discuss these exciting findings and identify several common principles by which nicotinic receptor activation modulates cortical circuits involved in cognition. Understanding how nicotine induces long-term changes in neuronal circuits and alters plasticity in the prefrontal cortex is essential to determining how these mechanisms interact to alter cognition.

  14. Jasmonate mediates salt-induced nicotine biosynthesis in tobacco (Nicotiana tabacum L.

    Directory of Open Access Journals (Sweden)

    Xiaodong Chen

    2016-04-01

    Full Text Available Jasmonate (JA, as an important signal, plays a key role in multiple processes of plant growth, development and stress response. Nicotine and related pyridine alkaloids in tobacco (Nicotiana tabacum L. are essential secondary metabolites. Whether environmental factors control nicotine biosynthesis and the underlying mechanism remains previously unreported. Here, we applied physiological and biochemical approaches to investigate how salt stress affects nicotine biosynthesis in tobacco. We found that salt stress induced the biosynthesis of JA, which subsequently triggered the activation of JA-responsive gene expression and, ultimately, nicotine synthesis. Bioinformatics analysis revealed the existence of many NtMYC2a-recognized G-box motifs in the promoter regions of NtLOX, NtAOS, NtAOC and NtOPR genes. Applying exogenous JA increased nicotine content, while suppressing JA biosynthesis reduced nicotine biosynthesis. Salt treatment could not efficiently induce nicotine biosynthesis in transgenic anti-COI1 tobacco plants. These results demonstrate that JA acts as the essential signal which triggers nicotine biosynthesis in tobacco after salt stress.

  15. Nicotine's defensive function in nature.

    Directory of Open Access Journals (Sweden)

    Anke Steppuhn

    2004-08-01

    Full Text Available Plants produce metabolites that directly decrease herbivore performance, and as a consequence, herbivores are selected for resistance to these metabolites. To determine whether these metabolites actually function as defenses requires measuring the performance of plants that are altered only in the production of a certain metabolite. To date, the defensive value of most plant resistance traits has not been demonstrated in nature. We transformed native tobacco(Nicotiana attenuata with a consensus fragment of its two putrescine N-methyl transferase (pmt genes in either antisense or inverted-repeat (IRpmt orientations. Only the latter reduced (by greater than 95% constitutive and inducible nicotine. With D(4-nicotinic acid (NA, we demonstrate that silencing pmt inhibits nicotine production, while the excess NA dimerizes to form anatabine. Larvae of the nicotine-adapted herbivore Manduca sexta (tobacco hornworm grew faster and, like the beetle Diabrotica undecimpunctata, preferred IRpmt plants in choice tests. When planted in their native habitat, IRpmt plants were attacked more frequently and, compared to wild-type plants, lost 3-fold more leaf area from a variety of native herbivores, of which the beet armyworm, Spodoptera exigua, and Trimerotropis spp. grasshoppers caused the most damage. These results provide strong evidence that nicotine functions as an efficient defense in nature and highlights the value of transgenic techniques for ecological research.

  16. Temperature-dependent dynamic mechanical properties of magnetorheological elastomers under magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Benxiang, E-mail: jubenxiang@qq.com [National Instrument Functional Materials Engineering Technology Research Center, Chongqing 400707 (China); Tang, Rui; Zhang, Dengyou; Yang, Bailian [National Instrument Functional Materials Engineering Technology Research Center, Chongqing 400707 (China); Yu, Miao; Liao, Changrong [College of Optoelectronic Engineering, Chongqing University, Chongqing 400044 (China)

    2015-01-15

    Both anisotropic and isotropic magnetorheological elastomer (MRE) samples were fabricated by using as-prepared polyurethane (PU) matrix and carbonyl iron particles. Temperature-dependent dynamic mechanical properties of MRE were investigated and analyzed. Due to the unique structural features of as-prepared matrix, temperature has a greater impact on the properties of as-prepared MRE, especially isotropic MRE. With increasing of temperature and magnetic field, MR effect of isotropic MRE can reach up to as high as 4176.5% at temperature of 80 °C, and the mechanism of the temperature-dependent in presence of magnetic field was discussed. These results indicated that MRE is a kind of temperature-dependent material, and can be cycled between MRE and MR plastomer (MRP) by varying temperature. - Highlights: • Both anisotropic and isotropic MRE were fabricated by using as-prepared matrix. • Temperature-dependent properties of MRE under magnetic field were investigated. • As-prepared MRE can transform MRE to MRP by adjusting temperature.

  17. Dynamic phase transitions in a cylindrical Ising nanowire under a time-dependent oscillating magnetic field

    International Nuclear Information System (INIS)

    Deviren, Bayram; Kantar, Ersin; Keskin, Mustafa

    2012-01-01

    The dynamic phase transitions in a cylindrical Ising nanowire system under a time-dependent oscillating external magnetic field for both ferromagnetic and antiferromagnetic interactions are investigated within the effective-field theory with correlations and the Glauber-type stochastic dynamics approach. The effective-field dynamic equations for the average longitudinal magnetizations on the surface shell and core are derived by employing the Glauber transition rates. Temperature dependence of the dynamic magnetizations, the dynamic total magnetization, the hysteresis loop areas and the dynamic correlations are investigated in order to characterize the nature (first- or second-order) of the dynamic transitions as well as the dynamic phase transition temperatures and the compensation behaviors. The system strongly affected by the surface situations. Some characteristic phenomena are found depending on the ratio of the physical parameters in the surface shell and the core. According to the values of Hamiltonian parameters, five different types of compensation behaviors in the Néel classification nomenclature exist in the system. The system also exhibits a reentrant behavior. - Highlights: ► The dynamic aspects of a cylindrical Ising nanowire are investigated in detail. ► The dynamic magnetizations, hysteresis loop areas and correlations are calculated. ► We studied both the FM and AFM interactions within the EFT with correlations. ► Some characteristic phenomena are found depending on the interaction parameters. ► We obtained five different types of compensation behaviors and reentrant behavior.

  18. Dynamic phase transitions in a cylindrical Ising nanowire under a time-dependent oscillating magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Deviren, Bayram [Department of Physics, Nevsehir University, 50300 Nevsehir (Turkey); Kantar, Ersin [Department of Physics, Erciyes University, 38039 Kayseri (Turkey); Keskin, Mustafa, E-mail: keskin@erciyes.edu.tr [Department of Physics, Erciyes University, 38039 Kayseri (Turkey)

    2012-07-15

    The dynamic phase transitions in a cylindrical Ising nanowire system under a time-dependent oscillating external magnetic field for both ferromagnetic and antiferromagnetic interactions are investigated within the effective-field theory with correlations and the Glauber-type stochastic dynamics approach. The effective-field dynamic equations for the average longitudinal magnetizations on the surface shell and core are derived by employing the Glauber transition rates. Temperature dependence of the dynamic magnetizations, the dynamic total magnetization, the hysteresis loop areas and the dynamic correlations are investigated in order to characterize the nature (first- or second-order) of the dynamic transitions as well as the dynamic phase transition temperatures and the compensation behaviors. The system strongly affected by the surface situations. Some characteristic phenomena are found depending on the ratio of the physical parameters in the surface shell and the core. According to the values of Hamiltonian parameters, five different types of compensation behaviors in the Neel classification nomenclature exist in the system. The system also exhibits a reentrant behavior. - Highlights: Black-Right-Pointing-Pointer The dynamic aspects of a cylindrical Ising nanowire are investigated in detail. Black-Right-Pointing-Pointer The dynamic magnetizations, hysteresis loop areas and correlations are calculated. Black-Right-Pointing-Pointer We studied both the FM and AFM interactions within the EFT with correlations. Black-Right-Pointing-Pointer Some characteristic phenomena are found depending on the interaction parameters. Black-Right-Pointing-Pointer We obtained five different types of compensation behaviors and reentrant behavior.

  19. A licence to vape: Is it time to trial of a nicotine licensing scheme to allow Australian adults controlled access to electronic cigarettes devices and refill solutions containing nicotine?

    Science.gov (United States)

    Gartner, Coral; Hall, Wayne

    2015-06-01

    Australia has some of the most restrictive laws concerning use of nicotine in e-cigarettes. The only current legal option for Australians to legally possess and use nicotine for vaping is with a medical prescription and domestic supply is limited to compounding pharmacies that prepare medicines for specific patients. An alternative regulatory option that could be implemented under current drugs and poisons regulations is a 'nicotine licensing' scheme utilising current provisions for 'dangerous poisons'. This commentary discusses how such a scheme could be used to trial access to nicotine solutions for vaping outside of a 'medicines framework' in Australia. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 27 CFR 21.119 - Nicotine solution.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b) Color...

  1. Cellular and synaptic mechanisms of nicotine addiction

    NARCIS (Netherlands)

    Mansvelder, H.D.; McGehee, D.S.

    2002-01-01

    The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors

  2. 21 CFR 172.310 - Aluminum nicotinate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be safely...

  3. Modeling the state dependent impulse control for computer virus propagation under media coverage

    Science.gov (United States)

    Liang, Xiyin; Pei, Yongzhen; Lv, Yunfei

    2018-02-01

    A state dependent impulsive control model is proposed to model the spread of computer virus incorporating media coverage. By the successor function, the sufficient conditions for the existence and uniqueness of order-1 periodic solution are presented first. Secondly, for two classes of periodic solutions, the geometric property of successor function and the analogue of the Poincaré criterion are employed to obtain the stability results. These results show that the number of the infective computers is under the threshold all the time. Finally, the theoretic and numerical analysis show that media coverage can delay the spread of computer virus.

  4. Frequent marijuana use is associated with greater nicotine addiction in adolescent smokers.

    Science.gov (United States)

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

    2014-08-01

    Marijuana and tobacco are the substances used most commonly by adolescents and co-occurring use is common. Use of one substance may potentiate the addictive properties of the other. The current study examined the severity of nicotine addiction among teen smokers as a function of co-occurring marijuana use. Participants were 165 adolescents (13-17 years old) who reported smoking at least 1 cigarette per day (CPD) in the past 30 days. General linear models examined the association of marijuana use with multiple measures of nicotine addiction including the Modified Fagerström Tolerance Questionnaire (mFTQ), Hooked on Nicotine Checklist (HONC), ICD-10, and the Nicotine Dependence Syndrome Scale (NDSS). The adolescent sample (mean age=16.1 years, SD=0.95) averaged 3.0 CPD (SD=3.0) for 1.98 years (SD=1.5). Most (79.5%) also smoked marijuana in the past 30 days. In models controlling for age, daily smoking status, and years of tobacco smoking, frequency of marijuana use accounted for 25-44% of the variance for all four measures of adolescent nicotine dependence. Marijuana use was associated with greater reported nicotine addiction among adolescent smokers. The findings suggest a role of marijuana in potentiating nicotine addiction and underscore the need for treatments that address both smoked substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. [Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia].

    Science.gov (United States)

    Figueroa, Catalina; Droppelmann, Katherine; Quiñones, Verónica; Amigo, Ludwig; Mendoza, Camila; Serrano, Valentina; Véjar, Margarita; Maiz, Alberto; Rigotti, Attilio

    2015-09-01

    Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

  6. Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite.

    Science.gov (United States)

    Costa-Rodrigues, Joao; Rocha, Isabel; Fernandes, Maria H

    2018-02-01

    Cigarette smoke is associated to pathological weakening of bone tissue, being considered an important playmaker in conditions such as osteoporosis and periodontal bone loss. In addition, it is also associated with an increased risk of failure in bone regeneration strategies. The present work aimed to characterize the effects of nicotine on human osteoclastogenesis over a hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or presence of the osteoclastogenesis enhancers M-CSF and RANKL, and were further treated with nicotine levels representative of the concentrations observed in the plasma and saliva of smokers. It was observed that nicotine at low concentrations elicit an increase in osteoclast differentiation, but only in the presence of M-CSF and RANKL it was also able to significantly increase the resorbing ability of osteoclasts. A slight downregulation of NFkB pathway and an increase in the production of TNF-α and, particularly PGE2, were involved in the observed effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects, causing a decrease in cell density. In conclusion, nicotine at levels found in the plasma of the smokers, has the ability to act directly on osteoclast precursors, inducing its osteoclastogenic differentiation. The stimulatory behavior appears to be dependent on the stage of osteoclastic differentiation of the precursor cells, which means, in the absence of M-CSF and RANKL, it only favors the initial stages of osteoclast differentiation, while in the presence of the growth factors, a significant increase in their resorbing ability is also achieved. © 2017 Wiley Periodicals, Inc.

  7. Angle-dependent light emission from aligned multiwalled carbon nanotubes under CO2 laser irradiation

    International Nuclear Information System (INIS)

    Zhang, Y; Gong, T; Liu, W J; Wei, J Q; Zhang, X F; Wang, K L; Zhong, M L; Wu, D H

    2007-01-01

    This paper reports the light emission from aligned multiwalled carbon nanotubes (MWNTs) under continuous wave CO 2 laser (λ = 10.6 μm) irradiation. Results indicate that the light emission is dependent on the angle θ between the laser incident direction and the nanotube axis. The relative intensity of the light emission at certain wavelengths shows a Lorentzian feature when θ varies from 0 0 to 90 0 . The Lorentzian fitting curve displays a distinct tendency between shorter (λ 700 nm). A minimum intensity was observed at θ m close to 67 0 under shorter wavelength, whereas a maximum intensity was shown at θ m of about 60 0 at longer wavelength. These results show the anisotropic property of aligned MWNTs

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

    Directory of Open Access Journals (Sweden)

    Tengfei eWang

    2014-12-01

    Full Text Available Menthol is preferred by approximately 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.