Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling

NEUROPHARMACOLOGY

卷:131

Article

Balla, Andrea¹  Dong, Bin²  Shilpa, Borehalli M.²  Vemuri, Kiran³  Makriyannis, Alexandros³  Pandey, Subhash C.^4,5  Sershen, Henry^1,6  Suckow, Raymond F.^2,7,8  Vinod, K. Yaragudri^2,9,10 

[1] Nathan S Kline Inst Psychiat Res, Dept Neurochem, New York, NY USA

[2] Nathan S Kline Inst Psychiat Res, Div Analyt Psychopharmacol, New York, NY USA

[3] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA

[4] Univ Illinois, Dept Psychiat, Ctr Alcohol Res Epigenet, Chicago, IL 60612 USA

[5] Jesse Brown VA Med Ctr, Chicago, IL USA

[6] NYU, Dept Psychiat, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA

[7] New York State Psychiat Inst & Hosp, New York, NY 10032 USA

[8] Columbia Univ Coll Phys & Surg, Dept Psychiat, 722 W 168th St, New York, NY 10032 USA

[9] Emot Brain Inst, New York, NY USA

[10] NYU, Dept Child & Adolescent Psychiat, Langone Med Ctr, New York, NY USA

关键词: Binge drinking;    Nucleus accumbens;    Cannabinoid receptor;    Neutral antagonist;    AM4113;   

DOI  :  10.1016/j.neuropharm.2017.10.040

来源: Elsevier

【 摘 要 】

Binge alcohol (ethanol) drinking is associated with profound adverse effects on our health and society. Rimonabant (SR141716A), a CB1 receptor inverse agonist, was previously shown to be effective for nicotine cessation and obesity. However, studies using rimonabant were discontinued as it was associated with an increased risk of depression and anxiety. In the present study, we examined the pharmacokinetics and effects of AM4113, a novel CBI receptor neutral antagonist on binge-like ethanol drinking in C57BL/6J mice using a two-bottle choice drinking-in-dark (DID) paradigm. The results indicated a slower elimination of AM4113 in the brain than in plasma. AM4113 suppressed ethanol consumption and preference without having significant effects on body weight, ambulatory activity, preference for tastants (saccharin and quinine) and ethanol metabolism. AM4113 pretreatment reduced ethanol-induced increase in dopamine release in nucleus accumbens. Collectively, these data suggest an important role of CBI receptor-mediated regulation of binge-like ethanol consumption and mesolimbic dopaminergic signaling, and further points to the potential utility of CBI neutral antagonists for the treatment of binge ethanol drinking. Published by Elsevier Ltd.

【 授权许可】

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