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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 D 1R appears to play a more prominent role than the D2R in the discriminative stimulus properties of (+)-MDMA.

Original languageEnglish (US)
Pages (from-to)326-336
Number of pages11
JournalPsychopharmacology
Volume173
Issue number3-4
DOIs
StatePublished - May 2004

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N-Methyl-3,4-methylenedioxyamphetamine
Dopamine
eticlopride
Locomotion
Serotonin
Sprague Dawley Rats

Keywords

  • 3,4-methylenedioxymethamphetamine
  • Dopamine receptors
  • Drug discrimination
  • Eticlopride
  • Hyperactivity
  • SCH 23390

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA. / Bubar, Marcy J.; Pack, Kami M.; Frankel, Paul S.; Cunningham, Kathryn.

In: Psychopharmacology, Vol. 173, No. 3-4, 05.2004, p. 326-336.

Research output: Contribution to journalArticle

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AB - 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 D 1R appears to play a more prominent role than the D2R in the discriminative stimulus properties of (+)-MDMA.

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