Metabotropic groupe glutamate receptors (mGluR) antagonist attenuate cocaine-induced toxicity and cocaine-induced behavioral sensitization in mice
Cocaine abuse and dependence is a worldwide health problem. However, there are no currently approved medications to reduce cocaine abuse/relapse and toxicity. Published data showed that group I mGluR antagonists (mGluR1 and mGluR5) possess an anti-addictive potential in various animal models of cocaine abuse. In the present study we assessed the impact of mGluR1 antagonist – EMQMCM and mGluR5 antagonist – MTEP on the cocaine-induced toxicity (lethality) in mice. Moreover, we evaluated the infl uence of these antagonists on motivational effect of cocaine measured in the sensitization test to its hyperlocomotor effect in mice. Our study indicated that EMQMCM and MTEP, at the doses of 2.5; 5, and 10 mg/kg, dose-dependently decreased cocaine-induced lethality produced by 75 mg/ kg of cocaine. The effect of EMQMCM was stronger than MTEP, and EMQMCM at the dose of 10 mg/kg completely reduced the lethality induced by cocaine. Furthermore, EMQMCM but not MTEP, signifi cantly reduced the expression of cocaine-induced (10 mg/kg) behavioral sensitization. Our results suggest that mGluR1 receptors are implicated in motivational effect of cocaine but both receptors (particularly mGluR1) play a role in cocaine-induced toxicity.