Serotonin antagonists fail to alter MDMA self-administration in rats

• Published in: Pharmacology, biochemistry and behavior Vol. 148; pp. 38 - 45
• Main Authors: Schenk, Susan, Foote, Jason, Aronsen, Dane, Bukholt, Natasha, Highgate, Quenten, Van de Wetering, Ross, Webster, Jeremy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2016
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Animals; Drug-Seeking Behavior - drug effects; Extinction, Psychological; Hyperactivity; Ketanserin - pharmacology; Male; MDMA; N-Methyl-3,4-methylenedioxyamphetamine - administration & dosage; Oxadiazoles - pharmacology; Piperazines - pharmacology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Reinstatement; Self Administration; Serotonin Antagonists - pharmacology; Serotonin receptors; Self-administration; Hyperactivity; Serotonin receptors; Reinstatement; MDMA
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2016.06.002

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. •MDMA self-administration was not decreased by several 5-HT antagonists.•MDMA-seeking was not decreased by several 5-HT antagonists.•MDMA-produced hyperactivity was decreased by 5-HT antagonists.•Cocaine-seeking was attenuated by some 5-HT antagonists.•MDMA-seeking was decreased by pretreatment with a 5-HT1A agonist.