Effects of Dopamine D1- or D2-like Receptor Antagonists on the Hypermotive and Discriminative Stimulus Effects of (+)-MDMA

Rationale: Both dopamine (DA) and serotonin (5-HT) release are evoked by (+)-MDMA; however, little is known of the contribution of DA D1- and D2-like receptors (D1R and D2R, respectively) in the behavioral effects of (+)-MDMA. OBJECTIVES. To test the hypothesis that a D1R or D2R antagonist would attenuate the hypermotive or discriminative stimulus effects of (+)-MDMA.

Methods: Male Sprague-Dawley rats (n=164) were pretreated with the D1R antagonist SCH 23390 (3.125-50 microg/kg, s.c.) or the D2R antagonist eticlopride (12.5-50 microg/kg, s.c.) prior to treatment with (+)-MDMA (3 mg/kg, s.c.) and locomotor activity was recorded using photobeam monitors. Twelve additional rats trained to discriminate (+)-MDMA (1 mg/kg, i.p.) from saline in a two-lever water-reinforced FR20 task were administered SCH 23390 (6.25 microg/kg, i.p.) or eticlopride (12.5 microg/kg, i.p.) prior to (+)-MDMA (0.375-1.0 mg/kg, i.p.). Rats were then placed in the drug discrimination chambers and the percent (+)-MDMA appropriate responding and response rate were measured.

Results: Both SCH 23390 and eticlopride blocked (+)-MDMA-evoked hyperactivity in a dose-related manner; the highest doses of the antagonists also effectively suppressed basal locomotor activity. In rats trained to discriminate (+)-MDMA from saline, SCH 23390 (6.25 microg/kg), but not eticlopride (12.5 microg/kg), blocked the stimulus effects of (+)-MDMA without altering response rate. CONCLUSION. These data indicate that DA released indirectly by (+)-MDMA administration results in stimulation of D1R and D2R to enhance locomotor activity. Furthermore, the D1R appears to play a more prominent role than the D2R in the discriminative stimulus properties of (+)-MDMA.