The effect of varenicline on binge-like ethanol consumption in mice is beta4 nicotinic acetylcholine receptor-independent

BACKGROUND: Our laboratory has previously shown that the smoking-cessation agent varenicline, an agonist/partial agonist of alpha4beta2, alpha3beta4, alpha3beta2, alpha6beta2 (* indicates the possibility of additional subunits) and alpha7 subunits of nicotinic acetylcholine receptors (nAChRs), reduces ethanol consumption in rats only after long-term exposure (12 weeks). As compounds having partial agonistic activity on alpha3beta4* nAChRs were shown to decrease ethanol consumption in rodents, we assessed here the involvement of the beta4 subunit in the effect of varenicline in the reduction of short- and long-term binge-like ethanol drinking in mice. METHODS: We used the well-validated drinking-in-the-dark (DID) paradigm to model chronic binge-like ethanol drinking in beta4-/- and beta4+/+ littermate mice and compare the effect of intraperitoneal injection of varenicline (2mg/kg) on ethanol intake following short- (4 weeks) or long-term (12 weeks) exposure. RESULTS: Drinking pattern and amounts of ethanol intake were similar in beta4-/- and beta4+/+ mice. Interestingly, our results showed that varenicline reduces ethanol consumption following short- and long-term ethanol exposure in the DID. Although the effect of varenicline on the reduction of ethanol consumption was slightly more pronounced in beta4-/- mice than their beta4+/+ littermates no significant differences were observed between genotypes. CONCLUSION: In mice, varenicline reduces binge-like ethanol consumption both after short- and long-term exposure in the DID and this effect is independent of beta4 nAChR subunit.