Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA) is often combined with ethanol (EtOH). The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze.

Adolescent OF1 mice were exposed to EtOH (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42). MDMA (10 or 20 mg/kg) was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42), resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured.

At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin.

The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood.