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Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA.
Psychopharmacology (Berl). 2004 May; 173(3-4):326-36.P

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 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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15064911

Citation

Bubar, Marcy J., et al. "Effects of Dopamine D1- or D2-like Receptor Antagonists On the Hypermotive and Discriminative Stimulus Effects of (+)-MDMA." Psychopharmacology, vol. 173, no. 3-4, 2004, pp. 326-36.
Bubar MJ, Pack KM, Frankel PS, et al. Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA. Psychopharmacology (Berl). 2004;173(3-4):326-36.
Bubar, M. J., Pack, K. M., Frankel, P. S., & Cunningham, K. A. (2004). Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA. Psychopharmacology, 173(3-4), 326-36.
Bubar MJ, et al. Effects of Dopamine D1- or D2-like Receptor Antagonists On the Hypermotive and Discriminative Stimulus Effects of (+)-MDMA. Psychopharmacology (Berl). 2004;173(3-4):326-36. PubMed PMID: 15064911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA. AU - Bubar,Marcy J, AU - Pack,Kami M, AU - Frankel,Paul S, AU - Cunningham,Kathryn A, Y1 - 2004/04/03/ PY - 2003/10/08/received PY - 2003/12/24/accepted PY - 2004/4/6/pubmed PY - 2004/12/16/medline PY - 2004/4/6/entrez SP - 326 EP - 36 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 173 IS - 3-4 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/15064911/Effects_of_dopamine_D1__or_D2_like_receptor_antagonists_on_the_hypermotive_and_discriminative_stimulus_effects_of__+__MDMA_ L2 - https://dx.doi.org/10.1007/s00213-004-1790-1 DB - PRIME DP - Unbound Medicine ER -