Recent studies demonstrated that the metabotropic glutamate receptor subtype 7 “mGluR7” activation may reduce motivational aspects of ethanol dependence. We investigated the role of mGlu7 receptor in ethanol-related behaviors using the allosteric agonist AMN082 in mice.
Results have shown that mGluR7 activation increased the sedative effect of ethanol as measured by the duration of loss of righting reflex (LORR) and reduced the severity of ethanol-induced withdrawal.
Importantly, the protective effect of the drug on alcohol-induced withdrawal was found when the AMN082 was injected before, but not after, injection of ethanol suggesting that mGluR7 activation prevented development of dependence rather than producing an anti-convulsant effect.
In addition, ethanol-induced locomotor stimulation was blocked by following mGluR7 activation.
Furthermore, mice injected with AMN082 consumed less ethanol in a two-bottle free-choice paradigm and in a drinking in the dark (DID) model. Impairment in reward mechanisms in AMN082-injected mice was confirmed by the lack of ethanol-induced conditioned place preference (CPP).
Follow-up control experiments have shown that plasma alcohol concentrations of AMN082 and vehicle-treated mice were similar.
Taken together, these findings provide evidence for the crucial role of mGluR7 in ethanol-related behaviors, especially in voluntary alcohol drinking and alcohol reward. Thus, pharmacological targeting mGluR7 with AMN082-like compounds might be a potential means to tackle ethanol abuse and alcoholism in the future.
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