Blocking 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.
Social defeat stress reduces the rewarding effects of MDMA in adult male mice, but not in adolescents. Adult mice exposed to social defeat before each MDMA conditioning session did not develop a conditioned place preference at either 1.25 or 10 mg/kg doses, indicating decreased sensitivity to MDMA reward. Social defeat did not alter the motor or anxiogenic effects of MDMA. Adult defeated mice had higher corticosterone levels than controls and adolescent mice. Social stress had no behavioral effects in adolescent mice, suggesting age-dependent vulnerability.