Metabotropic glutamate 5 receptors regulate sensitivity to ethanol in mice
The International Journal of Neuropsychopharmacology (2008), 11: 765-774


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 (1 g/kg), a phenomenon not observed in wild-type littermates, suggesting increased sensitivity to the rewarding effects of ethanol in mutant mice.

Finally, mGlu5-deficient mice were more sensitive to ethanol-induced hypnosis at a high dose (3.5 g/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.

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