Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine
Susan Schenk, Quenten Highgate
Behavioural Pharmacology June 1, 2019 Peer reviewed DOI: 10.1097/fbp.0000000000000442
Summary
The discriminative stimulus effects of a higher dose of MDMA (3.0 mg/kg) involve both dopamine and serotonin mechanisms, but either can independently sustain these effects. In a study with rats trained to distinguish between AMPH (0.5 mg/kg) and MDMA (3.0 mg/kg), dopamine antagonists reduced AMPH discrimination without affecting MDMA, while serotonin antagonists had no impact on either drug's effects. This indicates that the MDMA stimulus can be maintained by either dopaminergic or serotonergic responses.
Study at a glance
| Design | experimental study |
|---|---|
| Population | rats trained for drug discrimination |
| Key finding | Dopamine antagonists decreased AMPH discrimination but did not affect MDMA discrimination, while serotonin antagonists did not alter the effects of either drug. |
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.