Effect of D1-like and D2-like receptor antagonists on methamphetamine and 3,4-methylenedioxymethamphetamine self-administration in rats

Abstract

It has been suggested that activation of dopamine D1-like and D2-like receptors contribute equally to the maintenance of drug self-administration. This study compared the contribution of these receptor subtypes to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) self-administration. Effects of pretreatment with the D2-like receptor antagonist, eticlopride (0.0, 0.0125, 0.025 or 0.05 mg/kg, intraperitoneal), on responding maintained by several doses of MDMA (0.5, 1.0 and 2.0 mg/kg/infusion) and MA (0.05, 0.1 and 0.2 mg/kg/infusion) were determined. As we have published data showing the effects of the D1-like receptor antagonist, SCH23390 (0.0, 0.01 or 0.02 mg/kg, subcutaneous), on MDMA self-administration, effects of this dose range on the MA dose-response curve were determined. In our previous study, 0.02 mg/kg SCH23390 produced a rightward shift in the MDMA dose response curve, whereas in the present results, this dose decreased responding maintained by most doses of MA. Eticlopride increased the responding maintained by most doses of MDMA but failed to alter MA self-administration. The present results suggest that both D1-like and D2-like receptors contribute to the maintenance of MDMA self-administration, whereas MA self-administration was more sensitive to D1-like receptor blockade.