Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol

Neuropharmacology. 2009 Mar;56(4):814-20. doi: 10.1016/j.neuropharm.2009.01.007.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / genetics*
  • Alcohol Drinking / psychology*
  • Animals
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Central Nervous System Depressants / adverse effects
  • Central Nervous System Depressants / pharmacokinetics
  • Central Nervous System Depressants / pharmacology*
  • Choice Behavior
  • Ethanol / adverse effects
  • Ethanol / pharmacokinetics
  • Ethanol / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Postural Balance / drug effects
  • Substance Withdrawal Syndrome / psychology
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / genetics*
  • Taste / drug effects


  • Central Nervous System Depressants
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Ethanol
  • capsazepine
  • Capsaicin