title: Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens.
abstract: The mechanisms underlying predisposition to alcohol abuse and alcoholism are poorly understood. In this study, we evaluated the role of cannabinoid (CB1) receptors in (i) voluntary alcohol consumption, and (ii) acute alcohol-induced dopamine (DA) release in the nucleus accumbens, using mice that lack the CB1 receptor gene (CB1-/-). CB1-/- mice exhibited dramatically reduced voluntary alcohol consumption, and completely lacked alcohol-induced DA release in the nucleus accumbens, as compared to wild-type mice. The gender difference, with female mice consuming significantly more alcohol than wild-type male mice, was observed in wild-type mice, whereas this gender difference was nonexistent in CB1 mutant male and female mice. There was also a significant gender difference, with the wild-type, heterozygous, and mutant females consuming significantly more liquid and food than wild-type, heterozygous and mutant males. However, the total volume of fluid consumption and food intake did not differ between wild-type, heterozygous, and mutant mice. These results strongly suggest that the CB1 receptor system plays an important role in regulating the positive reinforcing properties of alcohol.
authors.affiliation: Division of Analytical Psychopharmacology, New York State Psychiatric Institute, New York, NY, USA. Hungund@nki.rfmh.org
authors.forename: Basalingappa L
authors.initials: BL
authors.lastname: Hungund
authors.forename: Istvan
authors.initials: I
authors.lastname: Szakall
authors.forename: Agota
authors.initials: A
authors.lastname: Adam
authors.forename: Balapal S
authors.initials: BS
authors.lastname: Basavarajappa
authors.forename: Csaba
authors.initials: C
authors.lastname: Vadasz
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000172:deficiency* / Q000235:genetics; D012646:Self Administration; D012737:Sex Factors; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000431:Ethanol; D004298:Dopamine