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Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA

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Abstract

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 μg/kg, SC) or the D2R antagonist eticlopride (12.5–50 μg/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 μg/kg, IP) or eticlopride (12.5 μg/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 μg/kg), but not eticlopride (12.5 μg/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.

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Acknowledgements

This research was supported by the National Institute on Drug Abuse DA 00260, DA 06057, DA 13595, and DA 15259. We would like to thank Robert G. Fox for his technical assistance. Also, we thank Jeffrey Burmeister, David Herin, and Erik Shank for their valuable comments and suggestions upon reviewing the manuscript. Portions of this work were presented at the annual meeting of The College on Problems of Drug Dependence held in Bal Harbour, Fla., in June, 2003.

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  1. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX , 77555-1031, USA

    Marcy J. Bubar, Kami M. Pack, Paul S. Frankel & Kathryn A. Cunningham

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  1. Marcy J. Bubar
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  2. Kami M. Pack
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Correspondence to Kathryn A. Cunningham.

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Bubar, M.J., Pack, K.M., Frankel, P.S. et al. Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA. Psychopharmacology 173, 326–336 (2004). https://doi.org/10.1007/s00213-004-1790-1

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