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

• Published in: Neuroscience letters Vol. 633; pp. 235 - 239
• Main Authors: Patkar, Omkar L., Belmer, Arnauld, Tarren, Josephine R., Holgate, Joan Y., Bartlett, Selena E.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28-10-2016
• Subjects: Animals; Binge Drinking - metabolism; Binge Drinking - therapy; Ethanol - blood; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Time Factors; Varenicline - therapeutic use
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.09.048

•Genetic ablation of β4 nicotinic acetylcholine receptor subunit does not affect ethanol drinking in mice in the drinking in the dark paradigm.•The acetylcholine receptor partial agonist varenicline reduces binge-like ethanol drinking following long-term exposure in mice.•The effect of varenicline in reducing binge-like ethanol drinking is independent of β4 nicotinic acetylcholine receptor subunit.
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.