Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol.
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.
Blednov
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YA
Waggoner Center for Alcohol and Addiction Research, University of Texas, 1 University Station A4800, Austin, TX 78712-0159, USA. yablednov@mail.utexas.edu
Harris
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RA
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
D002492:Central Nervous System Depressants; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000431:Ethanol; C071423:capsazepine; D002211:Capsaicin
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