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Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine.
Behav Pharmacol. 2019 06; 30(4):327-334.BP

Abstract

Most studies on discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) have been conducted using a relatively low dose (1.5 mg/kg), and those studies have invariably implicated serotonergic mechanisms. In contrast, dopaminergic mechanisms mediate the discriminative stimulus effects of amphetamine (AMPH). Some studies have suggested that the discriminative stimulus effects of a higher (3.0 mg/kg) dose of MDMA might rely on both serotonergic and dopaminergic mechanisms. This study aimed to determine effects of selective dopamine (DA) and serotonin (5HT) antagonists on the discriminative stimulus properties of AMPH (0.5 mg/kg) and MDMA (3.0 mg/kg). Separate groups of rats were trained to discriminate AMPH (0.5 mg/kg) or MDMA (3.0 mg/kg) from saline using a food-reinforced drug-discrimination procedure. Effects of DA (SCH 23390: 0.003-0.03 mg/kg and eticlopride: 0.03-0.3 mg/kg) or 5HT (ritanserin: 1.0-10.0 mg/kg, WAY-100635: 0.3-1.0 mg/kg and GR129375: 1.0-3.0 mg/kg) antagonists on the discriminative stimulus effects of both drugs were determined. Both DA antagonists dose-dependently decreased the AMPH but not the MDMA discrimination. None of the 5HT antagonists altered the discriminative stimulus effects of either drug. The MDMA (3.0 mg/kg) stimulus comprises both a DAergic and 5HTergic response, and the results suggest that either one is sufficient, but not required, to maintain the stimulus effects.

Authors+Show Affiliations

School of Psychology, Victoria University of Wellington, Wellington, New Zealand.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30199389

Citation

Schenk, Susan, and Quenten Highgate. "Dopamine and Serotonin Antagonists Fail to Alter the Discriminative Stimulus Properties of ±methylenedioxymethamphetamine." Behavioural Pharmacology, vol. 30, no. 4, 2019, pp. 327-334.
Schenk S, Highgate Q. Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine. Behav Pharmacol. 2019;30(4):327-334.
Schenk, S., & Highgate, Q. (2019). Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine. Behavioural Pharmacology, 30(4), 327-334. https://doi.org/10.1097/FBP.0000000000000442
Schenk S, Highgate Q. Dopamine and Serotonin Antagonists Fail to Alter the Discriminative Stimulus Properties of ±methylenedioxymethamphetamine. Behav Pharmacol. 2019;30(4):327-334. PubMed PMID: 30199389.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine. AU - Schenk,Susan, AU - Highgate,Quenten, PY - 2018/9/11/pubmed PY - 2020/2/14/medline PY - 2018/9/11/entrez SP - 327 EP - 334 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 30 IS - 4 N2 - Most studies on discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) have been conducted using a relatively low dose (1.5 mg/kg), and those studies have invariably implicated serotonergic mechanisms. In contrast, dopaminergic mechanisms mediate the discriminative stimulus effects of amphetamine (AMPH). Some studies have suggested that the discriminative stimulus effects of a higher (3.0 mg/kg) dose of MDMA might rely on both serotonergic and dopaminergic mechanisms. This study aimed to determine effects of selective dopamine (DA) and serotonin (5HT) antagonists on the discriminative stimulus properties of AMPH (0.5 mg/kg) and MDMA (3.0 mg/kg). Separate groups of rats were trained to discriminate AMPH (0.5 mg/kg) or MDMA (3.0 mg/kg) from saline using a food-reinforced drug-discrimination procedure. Effects of DA (SCH 23390: 0.003-0.03 mg/kg and eticlopride: 0.03-0.3 mg/kg) or 5HT (ritanserin: 1.0-10.0 mg/kg, WAY-100635: 0.3-1.0 mg/kg and GR129375: 1.0-3.0 mg/kg) antagonists on the discriminative stimulus effects of both drugs were determined. Both DA antagonists dose-dependently decreased the AMPH but not the MDMA discrimination. None of the 5HT antagonists altered the discriminative stimulus effects of either drug. The MDMA (3.0 mg/kg) stimulus comprises both a DAergic and 5HTergic response, and the results suggest that either one is sufficient, but not required, to maintain the stimulus effects. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/30199389/Dopamine_and_serotonin_antagonists_fail_to_alter_the_discriminative_stimulus_properties_of_±methylenedioxymethamphetamine_ L2 - https://doi.org/10.1097/FBP.0000000000000442 DB - PRIME DP - Unbound Medicine ER -