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

ABSTRACT: Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action plays a 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 identified. 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. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

SUBMITTER: Fowler CD

PROVIDER: S-EPMC3858456 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Fowler Christie D CD Kenny Paul J PJ

Neuropharmacology 20130918

Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action plays a 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 e ...[more]

PMID: 24055497

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Project description:INTRODUCTION:This study investigated the effects of nicotine/tobacco on neural activation during performance of a monetary incentive delay task. AIMS AND METHODS:Prior to each scan, nonsmokers received nicotine or placebo nasal spray, and smokers were smoking satiated or 24-hour withdrawn. During the scan, participants made timed responses to reward-related cues and received feedback. Parameter estimates from cue- and feedback-related activation in medial prefrontal regions and the nucleus accumbens were extracted and underwent within- and between-group analyses. Smokers' nicotine dependence severity was included as a continuous predictor variable for neural activation. RESULTS:Among smokers (n = 21), withdrawal decreased cue-related activation in the supplementary motor area and ventromedial prefrontal cortex, and the difference in activation (satiety > withdrawal) in these regions negatively correlated with nicotine dependence severity (Fagerström Test for Nicotine Dependence). Among nonsmokers (n = 22), nicotine increased the difference in nucleus accumbens activation between rewarded and nonrewarded feedback phases. Tobacco withdrawal and acute nicotine also had widespread effects on activation throughout the brain during the feedback phase. CONCLUSIONS:Acute nicotine in nonsmokers may have increased the salience of feedback information, but produced few effects on reward-related activation overall, perhaps reflecting nicotine's modest, indirect effects on reward processing. Conversely, tobacco withdrawal decreased activation compared with satiety, and this difference between conditions correlated with nicotine dependence severity. This suggests that as smokers become more dependent on nicotine, tobacco withdrawal has a more pronounced effect on reward processing. IMPLICATIONS:Relative to the acute effects of nicotine in nonsmokers, withdrawal from daily tobacco use had more significant effects on reward-related brain activation. This study suggests that the effects of tobacco withdrawal on reward-related brain function interact with subjects' level of nicotine dependence severity. These are potentially important sources of variability that could contribute to smoking cessation outcomes.

Dataset Information

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

Publications

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

Similar Datasets

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