In mice, a low dose of the cannabinoid agonist WIN 55,212-2 increased the rewarding effects of a low dose of MDMA, while a higher dose of the cannabinoid decreased the preference induced by higher MDMA doses. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose. Animals given the highest WIN dose plus a non-neurotoxic MDMA dose showed decreases in striatal dopamine and cortical serotonin. WIN-induced conditioned place preference was reinstated by MDMA priming, but WIN did not reinstate MDMA-induced preference. The findings indicate the cannabinoid system influences MDMA's rewarding effects and suggest potential neurotoxic effects when cannabinoids are combined with MDMA.
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.