TY - JOUR
T1 - The α3β4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL/6J mice
AU - Miller, Carley N.
AU - Ruggery, Colton
AU - Kamens, Helen M.
N1 - Funding Information:
Funding: This work was supported by The Broadhurst Career Development Professorship for the study of Health Promotion and Disease Prevention (HMK) , the Penn State Social Science Research Institute (HMK) , and an Erickson Discovery Grant (CR).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.alcohol.2018.11.006
DO - 10.1016/j.alcohol.2018.11.006
M3 - Article
C2 - 30496781
AN - SCOPUS:85063456838
SN - 0741-8329
VL - 79
SP - 1
EP - 6
JO - Alcohol
JF - Alcohol
ER -
