Serotonin antagonists fail to alter MDMA self-administration in rats.
Susan Schenk, Jason Foote, Dane Aronsen, Natasha Bukholt, Quenten Highgate, Ross Van de Wetering, Jeremy I Webster
Pharmacology, Biochemistry, and Behavior September 2016 DOI: 10.1016/j.pbb.2016.06.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA WAY 100635 GR 127935 ketanserin 8-OH-DPAT RU 24969 cocaine |
| Dose | MDMA 10.0 mg/kg ip; WAY 100635 0.1-1.0 mg/kg; GR 127935 1.0-3.0 mg/kg; ketanserin 1.0-3.0 mg/kg; 8-OH-DPAT 0.1-1.0 mg/kg; RU 24969 0.3-3.0 mg/kg |
| Topics | MDMA Serotonin |
| Keywords | Hyperactivity Reinstatement Self-administration Serotonin receptors |
| Key findings | Antagonists at 5-HT1A, 5-HT1B, and 5-HT2A receptors did not alter MDMA self-administration or MDMA-primed reinstatement, suggesting a limited role for these receptor mechanisms in MDMA-taking. However, the 5-HT1A agonist 8-OH-DPAT decreased cue-induced MDMA-seeking, which the authors propose may indicate that 5-HT1A agonists could serve as adjuncts to limit relapse to MDMA use. |
Abstract
Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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- Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) and R(-) MDMA on actigraphy-based daytime activity and sleep parameters in rhesus monkeys. Experimental and Clinical Psychopharmacology June 25, 2018
- Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine Behavioural Pharmacology June 1, 2019
and 3 more in the library
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