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Psychopharmacology (Berl). 2011 Feb;213(4):715-22. doi: 10.1007/s00213-010-2024-3. Epub 2010 Oct 6.

Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration.

Author information

1
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA. ogeorge@scripps.edu

Abstract

RATIONALE:

Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine. Varenicline, a partial α4β2 nicotinic acetylcholine receptor (nAChR) agonist, is effective in reducing nicotine craving and relapse in smokers, suggesting that α4β2 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 α4β2 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.

PMID:
20924754
PMCID:
PMC3033995
DOI:
10.1007/s00213-010-2024-3
[Indexed for MEDLINE]
Free PMC Article
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