Effect of SCH 23390 on (+/-)-3,4-methylenedioxymethamphetamine hyperactivity and self-administration in rats.

Recently, we demonstrated that (+/-)-3,4-methylenedioxymethamphetamine (MDMA; ecstasy) was reliably and dose-dependently self-administered by previously drug-naïve laboratory rats. The neurochemical basis of MDMA self-administration has not, however, been extensively studied. The present study investigated the role of dopamine in MDMA self-administration and hyperactivity. Pretreatment with the D1-like antagonist, SCH 23390 (0.01-0.08 mg/kg) produced a dose-dependent attenuation of MDMA (20.0 mg/kg)-produced hyperactivity. In self-administration tests, the baseline rate of responding maintained by intravenous infusions varied inversely with MDMA dose; as the dose available was changed, responding also changed so that about 10.0 mg/kg MDMA was self-administered during each daily 2-h session. Pretreatment with SCH 23390 (0.02 mg/kg) produced a rightward shift in the MDMA dose-response curve. These findings suggest that MDMA self-administration, like self-administration of other drugs of abuse, is dependent on the activation of dopaminergic substrates.