Ethanol–ecstasy (MDMA) interactions in rats: Preserved attenuation of hyperthermia and potentiation of hyperactivity by ethanol despite prior ethanol treatment

Recreational use of ecstasy, or (±)-3,4-methylenedioxymethamphetamine (MDMA), is often associated with other drugs, among which ethanol is one of the most common. Little is known, however, about the interaction between these two drugs. Using a daily ethanol and/or MDMA administration regimen, we recently showed that ethanol potentiated the hyperactivity (in the home cage), but attenuated the hyperthermia induced by MDMA. The prevention of hyperthermia occurred only on the first of four daily ethanol–MDMA treatments, indicating possible tolerance to ethanol. In order to test the tolerance hypothesis, we treated Long-Evans adult male rats with ethanol on 4 consecutive days prior to their first treatment with MDMA–ethanol. Our results first confirmed that ethanol (1.5 g/kg, i.p.) potentiates the psychomotor effects of MDMA (10 mg/kg, i.p.), while attenuating its pyretic effects (6.6 mg/kg, i.p.). The results also showed that both the potentiation of locomotor activity and the attenuation of hyperthermia by ethanol are not at all altered by prior ethanol treatment. This indicates that tolerance to ethanol per se does not account for what appears to be tolerance to the ethanol–MDMA combination, thus indicating that ethanol–MDMA combination likely has unique pharmacological effects.