Metabotropic glutamate 5 receptors regulate sensitivity to ethanol in mice

Int J Neuropsychopharmacol. 2008 Sep;11(6):765-74. doi: 10.1017/S1461145708008572. Epub 2008 Apr 10.

Abstract

The metabotropic glutamate receptor 5 (mGlu5) has been implicated in ethanol- and drug-seeking behaviours in rodent studies. Here we examine a number of ethanol-related behavioural assays in mice lacking mGlu5 and wild-type littermates. In a two-bottle free-choice paradigm, mGlu5-deficient mice consumed less ethanol with a reduced preference compared to wild-type mice. Indeed, mGlu5-deficienct mice were ethanol-avoiding at both concentrations of ethanol proffered (5% and 10% v/v). However, there was no difference in the rate of hepatic ethanol and acetaldehyde metabolism between genotypes and consumption of saccharin was similar. In a conditioned place preference study, mGlu5-deficient mice displayed a place preference for ethanol when conditioned with a low dose (1g/kg) of ethanol. Thus, while mGlu5-deficient mice consume less ethanol (with a reduced preference) than wild-type mice, this is not apparently related to impaired hepatic metabolism or a lack of reward from ethanol. Rather, we provide evidence that deletion of the mGlu5 receptor increases sensitivity to centrally mediated effects of ethanol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / metabolism
  • Aldehyde Dehydrogenase / metabolism
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology*
  • Central Nervous System Depressants / pharmacology*
  • Choice Behavior / drug effects
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / deficiency
  • Receptors, Metabotropic Glutamate / physiology*
  • Reflex / drug effects
  • Reflex / genetics

Substances

  • Central Nervous System Depressants
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Ethanol
  • Alcohol Dehydrogenase
  • Aldehyde Dehydrogenase