Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA
María Pilar García-pardo, Carla Escobar-Valero, Marta Rodrı́guez-arias, José Miñarro, M.a. Aguilar
Behavioural Pharmacology May 14, 2015 DOI: 10.1097/fbp.0000000000000138 via OpenAlex
Summary
AI-generated from the abstractBlocking NMDA glutamate receptors with memantine prevents mice from learning to prefer a place associated with MDMA (ecstasy) and also prevents a single dose of MDMA from re-establishing that preference after it has been extinguished. Memantine did not block preference for a chocolate-associated place and only partly reversed MDMA's memory-impairing effects. The results suggest that NMDA receptors are critical for both the initial rewarding effect of MDMA and for relapse-like behavior, indicating memantine as a potential treatment for MDMA abuse.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adolescent male mice |
| Interventions | Memantine MDMA |
| Dose | 1 or 10 mg/kg MDMA; 5 or 10 mg/kg memantine |
| Topics | Addiction MDMA |
| Keywords | Conditioned place preference Memantine Nmda receptor Extinction optical mineralogy |
| Citations | 29 |
| Key finding | Memantine blocked both the acquisition and the priming-induced reinstatement of MDMA-induced conditioned place preference in mice. |
Abstract
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 10 mg/kg MDMA and pretreated with 5 or 10 mg/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.