Interactions between ethanol and cocaine,amphetamine, or MDMA in the rat: thermoregulatory and locomotor effects

Rationale (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is often taken recreationally with ethanol (EtOH). In rats, EtOH may potentiate MDMA-induced hyperactivity, but attenuate hyperthermia. Objective Experiment 1 compared the interactions between EtOH (1.5 g/kg) and MDMA (6.6 mg/kg) with EtOH + cocaine (COCA; 10 mg/kg) and EtOH + amphetamine (AMPH; 1 mg/kg) on locomotor activity and thermoregulation. Experiment 2 used a weaker dose of MDMA (3.3 mg/kg) and larger doses of COCA (20 mg/kg) and AMPH (2 mg/kg). Materials and methods Drug treatments were administered on four occasions (2, 5, and 2 days apart, respectively; experiment 1) or two (2 days apart; experiment 2). Results All psychostimulants increased activity, and EtOH markedly increased the effect of MDMA. AMPH alone-related hyperactivity showed modest sensitization across treatment days, while MDMA + EtOH activity showed marked sensitization. AMPH, COCA, and MDMA induced hyperthermia of comparable amplitude (+1 to +1.5°C). Co-treatment with EtOH and AMPH (1 mg/kg) or COCA (10 mg/kg) produced hypothermia greater than that produced by EtOH alone. Conversely, EtOH attenuated MDMA-related hyperthermia, an effect increasing across treatment days. These results demonstrate that the interaction between MDMA and EtOH may be different from the interaction between EtOH and AMPH or COCA. Conclusion Because of potential health-related consequences of such polydrug misuse, it is worth identifying the mechanisms underlying these interactions, especially between EtOH and MDMA. Given the different affinity profiles of the three drugs for serotonin, dopamine, and norepinephrine transporters, our results appear compatible with the possibility of an important role of serotonin in at least the EtOH-induced potentiation of MDMA-induced hyperlocomotion.