Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine
Susan Schenk, Quenten Highgate
Behavioural Pharmacology June 1, 2019 DOI: 10.1097/fbp.0000000000000442
Summary
AI-generated from the abstractRats trained to recognize a high dose (3.0 mg/kg) of MDMA or amphetamine (0.5 mg/kg) were given drugs that block dopamine or serotonin receptors. Dopamine blockers reduced the rats' ability to recognize amphetamine but not MDMA. Serotonin blockers had no effect on either drug's recognition. The findings suggest that the high-dose MDMA stimulus involves both dopamine and serotonin systems, and either system alone is enough to maintain the drug's effects.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | SCH 23390 eticlopride ritanserin WAY-100635 GR129375 |
| Dose | MDMA: 3.0 mg/kg; AMPH: 0.5 mg/kg; SCH 23390: 0.003–0.03 mg/kg; eticlopride: 0.03–0.3 mg/kg; ritanserin: 1.0–10.0 mg/kg; WAY-100635: 0.3–1.0 mg/kg; GR129375: 1.0–3.0 mg/kg |
| Citations | 2 |
| Key finding | Dopamine antagonists decreased amphetamine but not MDMA discrimination, and serotonin antagonists did not alter either drug's discriminative stimulus effects, indicating that the high-dose MDMA stimulus involves both dopamine and serotonin systems and either is sufficient to maintain the effects. |
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.