title: Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor.
abstract: We have shown previously that voluntary ethanol consumption and resistance to ethanol-induced sedation are inversely related to neuropeptide Y (NPY) levels in NPY-knock-out (NPY(-/-)) and NPY-overexpressing mice. In the present report, we studied knock-out mice completely lacking the NPY Y1 receptor (Y1(-/-)) to further characterize the role of the NPY system in ethanol consumption and neurobiological responses to this drug. Here we report that male Y1(-/-) mice showed increased consumption of solutions containing 3, 6, and 10% (v/v) ethanol when compared with wild-type (Y1(+/+)) control mice. Female Y1(-/-) mice showed increased consumption of a 10% ethanol solution. In contrast, Y1(-/-) mice showed normal consumption of solutions containing either sucrose or quinine. Relative to Y1(+/+) mice, male Y1(-/-) mice were found to be less sensitive to the sedative effects of 3.5 and 4.0 gm/kg ethanol as measured by more rapid recovery from ethanol-induced sleep, although plasma ethanol levels did not differ significantly between the genotypes. Finally, male Y1(-/-) mice showed normal ethanol-induced ataxia on the rotarod test after administration of a 2.5 gm/kg dose. These data suggest that the NPY Y1 receptor regulates voluntary ethanol consumption and some of the intoxicating effects caused by administration of ethanol.
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3270, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
authors.forename: Ming Teng
authors.initials: MT
authors.lastname: Koh
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004351:Drug Resistance / Q000235:genetics; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D011803:Quinine / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D013395:Sucrose / Q000494:pharmacology
chemical_list: D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D000431:Ethanol; D013395:Sucrose; D011803:Quinine