Effects of dopamine D(1)- or D(2)-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA
Bubar MJ, Pack KM, Frankel PS, Cunningham KA.
Department of Pharmacology and Toxicology,
University of Texas Medical Branch,
77555-1031, Galveston, TX, USA.
Psychopharmacology (Berl). 2004 Apr 3
ABSTRACTRATIONALE. Both dopamine (DA) and serotonin (5-HT) release are evoked by (+)-MDMA; however, little is known of the contribution of DA D(1)- and D(2)-like receptors (D(1)R and D(2)R, respectively) in the behavioral effects of (+)-MDMA. OBJECTIVES. To test the hypothesis that a D(1)R or D(2)R antagonist would attenuate the hypermotive or discriminative stimulus effects of (+)-MDMA. METHODS. Male Sprague-Dawley rats ( n=164) were pretreated with the D(1)R antagonist SCH 23390 (3.125-50 microg/kg, SC) or the D(2)R antagonist eticlopride (12.5-50 microg/kg, SC) prior to treatment with (+)-MDMA (3 mg/kg, SC) and locomotor activity was recorded using photobeam monitors. Twelve additional rats trained to discriminate (+)-MDMA (1 mg/kg, IP) from saline in a two-lever water-reinforced FR20 task were administered SCH 23390 (6.25 microg/kg, IP) or eticlopride (12.5 microg/kg, IP) prior to (+)-MDMA (0.375-1.0 mg/kg, IP). 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 D(1)R and D(2)R to enhance locomotor activity. Furthermore, the D(1)R appears to play a more prominent role than the D(2)R in the discriminative stimulus properties of (+)-MDMA.D1
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