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

Autor: Balla A; Department of Neurochemistry, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States., Dong B; Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States., Shilpa BM; Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States., Vemuri K; Center for Drug Discovery, Northeastern University, Boston, MA, United States., Makriyannis A; Center for Drug Discovery, Northeastern University, Boston, MA, United States., Pandey SC; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, IL, United States., Sershen H; Department of Neurochemistry, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States; Department of Psychiatry, NYU Langone Medical Center, New York, NY, United States., Suckow RF; Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States; New York State Psychiatric Institute, New York, United States; Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, United States., Vinod KY; Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States; Emotional Brain Institute, Orangeburg, New York, NY, United States; Department of Child and Adolescent Psychiatry, NYU Langone Medical Center, New York, NY, United States. Electronic address: vyaragudri@nki.rfmh.org.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2018 Mar 15; Vol. 131, pp. 200-208. Date of Electronic Publication: 2017 Nov 03.
DOI: 10.1016/j.neuropharm.2017.10.040
Abstrakt: 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 CB1 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 CB1 receptor-mediated regulation of binge-like ethanol consumption and mesolimbic dopaminergic signaling, and further points to the potential utility of CB1 neutral antagonists for the treatment of binge ethanol drinking.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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