1. Metabotropic glutamate 5 receptors regulate sensitivity to ethanol in mice.
- Author
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Bird MK, Kirchhoff J, Djouma E, and Lawrence AJ
- Subjects
- Alcohol Dehydrogenase metabolism, Aldehyde Dehydrogenase metabolism, Analysis of Variance, Animals, Choice Behavior drug effects, Conditioning, Operant drug effects, Conditioning, Operant physiology, Dose-Response Relationship, Drug, Liver drug effects, Liver metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptor, Metabotropic Glutamate 5, Receptors, Metabotropic Glutamate deficiency, Reflex drug effects, Reflex genetics, Behavior, Animal drug effects, Behavior, Animal physiology, Central Nervous System Depressants pharmacology, Ethanol pharmacology, Receptors, Metabotropic Glutamate physiology
- 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.
- Published
- 2008
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