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In experimental animals, administration of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) leads to extensive, but incomplete, loss of 5-hydroxytryptamine (5-HT) innervation in the brain. Here, we report the effects of MDMA on 5-HT neuronal function measured in the rat in vivo using electrophysiological and microdialysis techniques. Two weeks after administration of an established neurotoxic regimen of MDMA (20 mg/kg s.c., twice daily for 4 days) we found; 1) no change in either the density or the firing activity of 5-HT neurons in the dorsal raphé nucleus; 2) no change in basal extracellular 5-HT in either the frontal cortex or the hippocampus, although extracellular 5-hydroxyindoleacetic acid was reduced by about 50% in both regions; and 3) no change in the amount of 5-HT released in the hippocampus in response to electrical stimulation (5 Hz) of either the dorsal or medial raphé nucleus, but a marked reduction in the amount of 5-HT released in the frontal cortex after electrical stimulation of the dorsal raphé nucleus. In summary, although MDMA causes marked 5-HT neurotoxicity, our data suggest that 5-HT cell firing is unchanged and, furthermore, that 5-HT release is maintained in some (but not all) forebrain regions even in response to physiological levels of stimulation.

Type

Journal article

Journal

J Pharmacol Exp Ther

Publication Date

10/1996

Volume

279

Pages

277 - 283

Keywords

Animals, Brain, Frontal Lobe, Hippocampus, Hydroxyindoleacetic Acid, Male, Microdialysis, N-Methyl-3,4-methylenedioxyamphetamine, Raphe Nuclei, Rats, Rats, Sprague-Dawley, Serotonin, Serotonin Agents