The α3β4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL6J mice.
Binge alcohol drinking is a health burden in the United States, which has an alarming economic impact. Unfortunately, medications available for alcohol abuse have low efficacy or adverse side effects, creating a need to evaluate novel therapies. Growing research suggests that 18-Methoxycoronaridine (18-MC), an α3β4 nicotinic acetylcholine receptor (nAChR) antagonist, may be effective at reducing ethanol consumption. However, its effects on binge-like ethanol consumption and other ethanol behaviors have not been examined. The present study examined the effect of α3β4 nAChRs antagonism on basal locomotor activity in male and female C57BL6J mice. Next we tested the effect of 18-MC on binge-like ethanol consumption, ethanol-induced sedation, and ethanol metabolism. Finally, we tested the effect of α3β4 nAChRs on saccharin consumption to ensure effects were specific for ethanol. We observed that 18-MC decreased binge-like ethanol consumption without altering saccharin consumption, the sedative effects of ethanol, or ethanol metabolism. High doses of 18-MC caused locomotor sedation in C57BL6J mice, but the effects were brief and likely did not contribute to differences in ethanol consumption. Our results support the involvement of the α3β4 nAChRs in binge-like ethanol intake, and further work should explore the use of 18-MC for treatment of alcohol use disorders.