Journal
PSYCHOPHARMACOLOGY
Volume 213, Issue 4, Pages 715-722Publisher
SPRINGER
DOI: 10.1007/s00213-010-2024-3
Keywords
Nicotine; alpha 4 beta 2 nicotinic receptor; Varenicline; Self-administration; Craving; Dependence
Categories
Funding
- Tobacco-Related Disease Research Program (TRDRP) from the State of California [17RT-0095]
- Pearson Center for Alcoholism and Addiction Research
- National Institute on Drug Abuse [DA12001, DA023597]
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Rationale Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine. Varenicline, a partial alpha 4 beta 2 nicotinic acetylcholine receptor (nAChR) agonist, is effective in reducing nicotine craving and relapse in smokers, suggesting that alpha 4 beta 2 nAChRs may play a key role in nicotine dependence. In rats, the effect of varenicline on nicotine intake has only been studied with limited access to the drug, a model of the positive reinforcing effect of nicotine. Varenicline has not been tested on the increase in motivation to take nicotine in nicotine-dependent rats. Objectives The present study evaluated the effects of varenicline on nicotine intake in rats with extended access to nicotine self-administration (23 h/day), a condition leading to the development of nicotine dependence. We hypothesized that varenicline's effects on nicotine self-administration would be greater in rats with extended than limited access to the drug and after forced abstinence rather than during baseline self-administration. Results Varenicline dose-dependently decreased nicotine self-administration in rats with limited (1 h/day) and extended (23 h/day) access. Despite an increased sensitivity to the motivational effects of abstinence on nicotine intake compared with limited-access rats, varenicline was equally effective in decreasing nicotine intake in dependent rats with extended access to nicotine. Conclusion These results suggest that alpha 4 beta 2 nAChRs are critical in mediating the positive reinforcing effects of nicotine but may not be a key element underlying the negative reinforcement process responsible for the increased nicotine intake after abstinence in dependent subjects.
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