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.
Adolescent mice pre-exposed to ethanol, MDMA, or both showed increased rewarding effects from a low dose of MDMA in a conditioned place preference model. Pre-exposure did not alter acquisition of place preference induced by a higher MDMA dose, but the preference was more persistent in mice pre-exposed to MDMA or ethanol plus the higher MDMA dose. After extinction, reinstatement occurred with lower priming doses in pre-exposed groups. Pre-treatment also caused long-term changes in brain monoamine levels, including dopamine turnover and serotonin metabolites, depending on the dose used. The findings suggest that adolescent exposure to ethanol and MDMA may enhance the addictive properties of MDMA.