Adolescent mice exposed to MDMA, cocaine, or both drugs showed lasting changes into adulthood in their response to MDMA. Only those pre-treated with MDMA alone developed a conditioned place preference for a low dose of MDMA. All groups developed preference for a higher dose, but extinction took longer in mice pre-treated with cocaine (46 sessions) or MDMA alone (28 sessions). Preference was reinstated with progressively lower priming doses in mice pre-treated with MDMA or cocaine alone. Early exposure to MDMA or cocaine induces long-lasting changes that modify adult responses to MDMA.
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.