The role of group I mGlu receptors in the expression of ethanol-induced conditioned place preference and ethanol withdrawal seizures in rats |
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Authors: | Kotlinska Jolanta H Bochenski Marcin Danysz Wojciech |
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Institution: | aDepartment of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland;bIn Vivo Pharmacology, R+D CNS, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318, Frankfurt am Main, Germany |
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Abstract: | In animal models, N-methyl-d-aspartate (NMDA) receptors antagonists inhibit physical dependence and the reinforcing effects of ethanol. The group I metabotropic glutamate (mGlu) receptors antagonists (mGlu1 and mGlu5) attenuate excitatory effect of glutamate by functional modulation of the glutamate/NMDA receptors. The objective of the present study was to evaluate the effects of a selective mGlu5 receptors antagonist—MTEP, and mGlu1 receptors antagonist—EMQMCM, on two processes relevant to alcohol addiction: the expression of ethanol-induced conditioned place preference (CPP) paradigm, and ethanol withdrawal audiogenic seizures in rats. Our experiments indicated that EMQMCM at the doses of 5 and 10 mg/kg, and MTEP at the doses of 2.5 and 5 mg/kg, significantly attenuated the expression of ethanol CPP. Furthermore, both group I mGlu receptor antagonists, i.e. EMQMCM at the dose of 10 mg/kg and MTEP at the dose of 5 mg/kg, attenuated audiogenic seizures induced by the sound stimulus 12 h after withdrawal of ethanol in dependent rats. Our study shows the importance of mGlu5 and mGlu1 receptors for the expression of ethanol-induced CPP and withdrawal seizures, although mGlu5 receptors antagonist (MTEP) was more potent than the antagonist of mGlu1 receptors (EMQMCM). |
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Keywords: | Ethanol Expression of CPP Withdrawal seizure Group I mGlu receptors antagonist EMQMCM MTEP |
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