The role of metabotropic glutamate receptor 7 (mGluR7) in drug dependence

Abstract

The successful pharmacotherapy for drug addiction is a challenge for pharmacology in XXI century. We still do not have any registered medication for cocaine by FDA, alcohol therapies are not enough successful. High hopes concern metabotropic glutamate 7 receptor as a target for pharmacotherapy development of drug dependence. It is well documented the role of the mGluR7 in rewarding and motivational effects of cocaine and alcohol. The mGluR7 allosteric agonist AMN082 and antagonist MMPIP have become new tools in preclinical studies. AMN082 attenuated cocaine-enhanced electrical Brain Stimulation Reward (eBSR) in rats and decreased cocaine self-administration too, probably by counteracting cocaine-induced inhibition of the ventral pallidal GABA release. The mGluR7 activation reduced alcohol intake and preference in rats. The mGluR7 receptors take part in reinstatement of drug-seeking behavior after abstinence. The investigations showed that AMN082 suppressed cocaine-induced reinstatement of self-administrated rats via mGluR2/3 mechanism. It was mentioned also that mGluR7 allosteric agonist inhibited reinstatement of ethanol-induced CPP. Moreover, activation of the mGluR7 receptor exhibits less adverse reaction in comparison to other mGluRs and may give a promise for further development of drug dependence therapies in humans. However, some nonspecific effects of the mGluR7 in ethanol addiction have been recognized, so there are further investigations needed to explain the mechanisms of the mGluR7 action in rewarding and motivational effects of drugs. © 2012 Curr. Issues Pharm. Med. Sci.