Adolescent pre‐exposure to ethanol and 3,4‐methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug‐induced reinstatement

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.

Study at a glance

Abstract

ABSTRACT Many adolescents often take ethanol (EtOH) in combination with 3,4‐methylenedioxymethylamphetamine (MDMA). In the present work, we used a mouse model to study the effect of repeated pre‐exposure during adolescence to EtOH (2 g/kg), MDMA (10 or 20 mg/kg) or EtOH + MDMA on the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm. Pre‐exposure to EtOH, MDMA or both increased the rewarding effects of a low dose of MDMA (1.25 mg/kg). These pre‐treatments did not affect the acquisition of the CPP induced by 5 mg/kg of MDMA. However, the CPP was more persistent in mice pre‐exposed to both doses of MDMA or to EtOH + MDMA20. After extinction of the CPP induced by 5 mg/kg of MDMA, reinstatement was observed in all groups with a priming dose of 2.5 mg/kg of MDMA, in the groups pre‐exposed to EtOH or MDMA alone with a priming dose of 1.25 mg/kg, and in the groups pre‐treated with MDMA alone with a priming dose of 0.625 mg/kg. Pre‐treatment during adolescence with MDMA or EtOH induced long‐term changes in the level of biogenic amines [dihydroxyphenyl acetic acid, homovanillic acid, dopamine turnover, serotonin (5‐hydroxytryptamine, 5‐HT) and 5‐hydroxyindole acetic acid (5‐HIAA) in the striatum, and 5‐HT and 5‐HIAA in the cortex] after the first reinstatement test, although these effects depended on the dose used during conditioning. These results suggest that exposure to EtOH and MDMA during adolescence reinforces the addictive properties of MDMA.