Serotonin antagonists fail to alter MDMA self-administration in rats.
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.
School of Psychology, Victoria University of Wellington, Wellington, New Zealand. Electronic address: susan.schenk@vuw.ac.nz.
Susan
S
Schenk
School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Jason
J
Foote
School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Dane
D
Aronsen
School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Natasha
N
Bukholt
School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Quenten
Q
Highgate
School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Ross
R
Van de Wetering
School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Jeremy
J
Webster
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; C090701:GR 127935; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine
Hyperactivity; MDMA; Reinstatement; Self-administration; Serotonin receptors