title: Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol.
abstract: The vanilloid receptor TRPV1 is activated by ethanol and this may be important for some of the central and peripheral actions of ethanol. To determine if this receptor has a role in ethanol-mediated behaviors, we studied null mutant mice in which the Trpv1 gene was deleted. Mice lacking this gene showed significantly higher preference for ethanol and consumed more ethanol in a two-bottle choice test as compared with wild type littermates. Null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol (2 g/kg). However, there were no differences between null mutant and wild type mice in severity of ethanol-induced acute withdrawal (4 g/kg) or conditioned taste aversion to ethanol (2.5 g/kg). Two behavioral phenotypes (decreased sensitivity to ethanol-induced sedation and faster recovery from ethanol-induced motor incoordination) seen in null mutant mice were reproduced in wild type mice by injection of a TRPV1 antagonist, capsazepine (10 mg/kg). These two ethanol behaviors were changed in the opposite direction after injection of capsaicin, a selective TRPV1 agonist, in wild type mice. The studies provide the first evidence that TRPV1 is important for specific behavioral actions of ethanol.
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, University of Texas, 1 University Station A4800, Austin, TX 78712-0159, USA. yablednov@mail.utexas.edu
authors.forename: Y A
authors.initials: YA
authors.lastname: Blednov
authors.forename: R A
authors.initials: RA
authors.lastname: Harris
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002755:Choice Behavior; D000431:Ethanol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004856:Postural Balance / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics*; D013649:Taste / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000431:Ethanol; C071423:capsazepine; D002211:Capsaicin
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