AMN082—a metabotropic glutamate receptor type 7 allosteric agonist in the NAc facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats

Abstract

Nucleus accumbens (NAc) plays a primary role in opioid reward. The actions of glutamate (which is the most extensive excitatory neurotransmitter in the mammalian central nervous system) are mediated through the activation of the ionotropic and metabotropic glutamate receptors (mGluRs). Previous studies have shown the extensive distributions of the different types of mGluRs, including mGluR7, in regions that are involved in opioid reward, such as NAc. In this study, CPP was used to investigate the effect of mGluR7 on the extinction period, and the reinstatement of morphine. The animals received bilaterally microinjections of AMN082, a selective mGluR7 allosteric agonist, into the NAc. In Experiment 1, the rats received AMN082 (1 and 5 μg/0.5 μl) during the extinction period. In Experiment 2, the CPP morphine-extinguished rats received AMN082 (1, 3 and 5 μg/0.5 μl) five minutes prior to the administration of an ineffective dosage of morphine (1 mg/kg) in order to reinstate the extinguished morphine. The results of the recorded conditioning scores in this study showed that the intra-accumbal administration of AMN08 reduced the extinction period of morphine. Moreover, the administration of AMN082 into the NAc dose-dependently inhibited the reinstatement of morphine. The findings suggested that the mGluR7 in the NAc facilitates the extinction and inhibits the reinstatement of the morphine-induced CPP that could have been mediated by an increase in the release of extracellular glutamate.