One-off liver directed AAV gene therapy achieves long term uptake of acid beta-glucocerebrosidase by macrophages of affected tissues in Gaucher disease

Abstract

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 C57BL/6J 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 C57BL/6J 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.