期刊
PSYCHOPHARMACOLOGY
卷 227, 期 2, 页码 287-298出版社
SPRINGER
DOI: 10.1007/s00213-013-2974-3
关键词
Varenicline; Cytisine; Alcohol; High-alcohol-drinking UChB rats; Ethanol preference
资金
- MSI [P10/063-F, P05/001-F]
- FONDECYT [111-0392]
Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied. This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB). Repeated dosing (0.5 or 1.0 mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10 % (v/v) ethanol and water 24 h/day for 4 weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2 % saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8-10 days induced tolerance to their effects on ethanol consumption. This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use.
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