Effects of (+)-fenfluramine on 3,4-methylenedioxymethamphetamine (MDMA) discrimination in rats

• Published in: Pharmacology, biochemistry and behavior Vol. 53; no. 2; pp. 455 - 461
• Main Authors: Baker, L.E., Makhay, M.M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.1996; Elsevier Science
• Subjects: (+)-Amphetamine; (+)-Fenfluramine; Animals; Biological and medical sciences; Dextroamphetamine - pharmacology; Discrimination (Psychology) - drug effects; Dopamine; Dopamine Agents - pharmacology; Dose-Response Relationship, Drug; Drug discrimination; Fenfluramine - pharmacology; Male; MDMA; Medical sciences; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Serotonin; Serotonin Agents - pharmacology; Drug discrimination; Dopamine; Serotonin; (+)-Fenfluramine; Rats; (+)-Amphetamine; MDMA; Amphetamine derivatives; Vertebrata; Agonist; Mammalia; Serotoninergic receptor; Rat; CNS stimulant; Animal; Rodentia; Discrimination task
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(95)02017-9

This study examined the effects of a presumed neurotoxic dose regimen of (+)-fenfluramine on the discrimination of MDMA and (+)-amphetamine in male Sprague-Dawley rats trained to discriminate 1.5 mg/kg MDMA from saline in a two-choice operant task. Substitution tests were conducted with saline, several doses of MDMA (0.19–1.5 mg/kg), and (+)-amphetamine (0.125–1.0 mg/kg) prior to and again following the administration of (+)-fenfluramine (4.0 mg/kg twice a day for 4 days; n = 11) or a similar pattern of saline injections ( n = 10). During pretreatment substitution tests, lower doses of MDMA elicited drug-appropriate responding in a dose-dependent manner, although none of these doses substituted for the training dose. Likewise, no dose of (+)-amphetamine substituted for the training drug during pretreatment substitution tests. The discrimination of MDMA was disrupted in some animals following (+)-fenfluramine treatment, but with subsequent training, discrimination criteria were met. In posttreatment substitution tests, the lowest dose of MDMA produced significantly higher drug-appropriate responding in (+)-fenfluramine treated animals but not in saline-treated animals. The amount of drug-appropriate responding during posttreatment substitution tests with (+)-amphetamine varied little from pretreatment substitution tests in saline-treated animals, but was greater at all doses in (+)-fenfluramine-treated animals; the highest dose of (+)-amphetamine substituted for MDMA subsequent to (+)-fenfluramine treatment. These results support previous findings that the long-lasting serotonergic effects of fenfluramine may have functional consequences that can be detected using a drug discrimination procedure. Specifically, serotonin depletion may unmask or strengthen the stimulant-like effects of MDMA.