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Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and release: Comparison between dorsal and median raphe 5-HT systems

Lookup NU author(s): Dr Sasha Gartside, Professor Richard McQuade


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It is proposed that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more toxic to 5-HT neurones projecting from the dorsal raphe nucleus (DRN) than to those from the median raphe nucleus (MRN). Since increased 5-HT release has been associated with MDMA-induced neurotoxicity, MDMA may have a DRN-selective 5-HT releasing effect. Here we have compared the effects of acute MDMA on DRN and MRN 5-HT pathways using in vivo electrophysiological and neurochemical techniques. MDMA inhibited the firing of 5-HT neurones in both the DRN and the MRN, and did so with similar potency (ED50 values, 0.589 +/- 0.151 (8) and 0.588 +/- 0.207 (6) mg/kg i.v., respectively). In both nuclei this inhibitory effect was reversed by the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.). Microdialysis measurements were made in the frontal cortex and dorsal hippocampus, regions which receive a DRN- and an MRN-selective 5-HT innervation, respectively. A dose of 1 mg/kg i.v. MDMA increased extracellular 5-HT 3-fold in both the frontal cortex and dorsal hippocampus. A higher dose (3 mg/kg i.v.) increased 5-HT levels 8-fold in both regions. Overall, our data suggest that MDMA releases 5-HT from the cell body and terminal regions of both DRN and MRN 5-HT pathways, and does so in a qualitatively and quantitatively similar fashion. We conclude that any DRN-selectivity in the neurotoxic effects of MDMA is not due to a DRN-selective, acute 5-HT releasing action of the drug.

Publication metadata

Author(s): Gartside SE, McQuade R, Sharp T

Publication type: Article

Publication status: Published

Journal: Neuropharmacology

Year: 1997

Volume: 36

Issue: 11-12

Pages: 1697-1703

Print publication date: 01/11/1997

ISSN (print): 0028-3908

ISSN (electronic): 1873-7064

Publisher: Pergamon


DOI: 10.1016/S0028-3908(97)00171-8

Notes: 0028-3908 (Print) Journal Article


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