Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA

Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-d-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10mg/kg MDMA and pretreated with 5 or 10mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In addition, the effects of memantine on acquisition of chocolate-induced CPP and the effects of memantine and MDMA on a passive avoidance task were evaluated. Memantine did not exert any motivational effects, but blocked the acquisition of MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP induced by priming with MDMA. Memantine did not block the CPP induced by chocolate, and it partially reversed the impairing effects of MDMA on memory. Our results demonstrate that NMDARs are involved in acquisition of the conditioned rewarding effects of MDMA and in priming-induced reinstatement of CPP following extinction. Moreover, they suggest the validity of memantine for the treatment of MDMA abuse.