p-Chloroamphetamine (PCA), 3,4-methylenedioxy-methamphetamine (MDMA) and d-fenfluramine pretreatment attenuates d-fenfluramine-evoked release of 5-HT in vivo.
Hugh Series, P J Cowen, Trevor Sharp
Psychopharmacology December 1994 DOI: 10.1007/bf02247485 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Rats treated with PCA, MDMA, d-fenfluramine, or vehicle, studied two weeks after treatment |
| Interventions | PCA MDMA d-fenfluramine KCl |
| Dose | d-fenfluramine 10 mg/kg IP (challenge), 1.25 mg/kg x 8 (pretreatment); MDMA 20 mg/kg x 8; KCl 100 mM via microdialysis probe |
| Duration | 2 weeks after treatment |
| Measures | Microdialysis measurement of basal and evoked 5-HT release |
| Topics | MDMA Serotonin |
| Key findings | The authors argue the data are consistent with the hypothesis that d-fenfluramine-evoked serotonin release occurs via terminals destroyed by PCA, MDMA, and d-fenfluramine pretreatment, whereas potassium chloride evokes release from both PCA-sensitive and PCA-insensitive terminals. d-Fenfluramine-evoked release fell by 90.9% after PCA, 45.2% after MDMA, and 72.0% after d-fenfluramine, compared with a smaller 66.8% reduction in potassium-evoked release after PCA. |
Abstract
Previous work has suggested that repeated treatment with substituted amphetamines including PCA, MDMA and d-fenfluramine produces a persistent neurodegeneration which is relatively selective for the fine serotoninergic terminals arising from the dorsal raphe nucleus. The aim of the present study was to investigate whether the acute releasing effect of d-fenfluramine might also be sensitive to lesions produced by PCA, MDMA and d-fenfluramine itself. Basal and 5-HT release evoked by d-fenfluramine or 100 mM KCl was measured by microdialysis in frontal or parietal cortex of rats 2 weeks after they had been treated with a neurodegenerative regime of PCA, MDMA, d-fenfluramine, or vehicle. In frontal cortex of vehicle controls, d-fenfluramine (10 mg/kg IP) and KCl (100 mM via microdialysis probe) evoked an increase in 5-HT of 1740% and 779% of basal, respectively. PCA pretreatment reduced d-fenfluramine-evoked 5-HT release by 90.9% while potassium-evoked release was reduced by only 66.8%. Similar results were obtained in parietal cortex. MDMA (20 mg/kg x 8) and d-fenfluramine (1.25 mg/kg x 8) pretreatment reduced d-fenfluramine-evoked release of 5-HT in frontal cortex by 45.2% and 72.0%, respectively. Overall, the present data are consistent with the hypothesis that the acute release of 5-HT evoked by d-fenfluramine occurs via those terminals destroyed by pretreatment with PCA, MDMA and d-fenfluramine, while KCl evokes release from both PCA-sensitive and PCA-insensitive terminals. The significance of these results for the interpretation of neuroendocrine data from d-fenfluramine challenge tests is discussed.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 6
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT Synapse 2001
- Behavioural and neuroendocrine responses to D-fenfluramine in rats treated with neurotoxic amphetamines Journal of Psychopharmacology May 1, 1995
- Neural and cardiac toxicities associated with 3,4-methylenedioxymethamphetamine (MDMA). International review of neurobiology 2009
- Tolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges. Neuroscience March 27, 2008
and 1 more in the library
Cites 6
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- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
- Lasting effects of (+-)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: neurochemical observations. Journal of Pharmacology and Experimental Therapeutics May 1, 1992
- Distinct morphologic classes of serotonergic axons in primates exhibit differential vulnerability to the psychotropic drug 3,4-methylenedioxymethamphetamine. Neuroscience 1989
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