Effects of (+)-fenfluramine on 3,4-methylenedioxymethamphetamine (MDMA) discrimination in rats.
Pharmacology, biochemistry, and behavior February 1996 DOI: 10.1016/0091-3057(95)02017-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 21 |
| Population | Male Sprague-Dawley rats trained to discriminate 1.5 mg/kg MDMA from saline |
| Interventions | (+)-Fenfluramine MDMA (+)-Amphetamine Saline |
| Dose | (+)-Fenfluramine 4.0 mg/kg twice a day for 4 days; MDMA 0.19-1.5 mg/kg; (+)-amphetamine 0.125-1.0 mg/kg; training dose MDMA 1.5 mg/kg |
| Duration | 4-day fenfluramine treatment; substitution tests before and after treatment |
| Topics | MDMA |
| Key findings | The authors report that a presumed neurotoxic fenfluramine regimen increased drug-appropriate responding to low-dose MDMA and to all tested amphetamine doses in rats trained to discriminate MDMA, with the highest amphetamine dose substituting for MDMA after treatment. They argue these results support the idea that fenfluramine's long-lasting serotonergic effects have functional consequences detectable by drug discrimination, and that serotonin depletion may unmask or strengthen MDMA's stimulant-like effects. |
Abstract
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.