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The effect of varenicline on binge-like ethanol consumption in mice is β4 nicotinic acetylcholine receptor-independent.

ABSTRACT

Our laboratory has previously shown that the smoking-cessation agent varenicline, an agonist/partial agonist of α4β2, α3β4, α3β2, α6β2 ( indicates the possibility of additional subunits) and α7 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 α3β4 nAChRs were shown to decrease ethanol consumption in rodents, we assessed here the involvement of the β4 subunit in the effect of varenicline in the reduction of short- and long-term binge-like ethanol drinking in mice.We used the well-validated drinking-in-the-dark (DID) paradigm to model chronic binge-like ethanol drinking in β4(-/-) and β4(+/+) 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.Drinking pattern and amounts of ethanol intake were similar in β4(-/-) and β4(+/+) 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 β4(-/-) mice than their β4(+/+) littermates no significant differences were observed between genotypes.In mice, varenicline reduces binge-like ethanol consumption both after short- and long-term exposure in the DID and this effect is independent of β4 nAChR subunit.