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Effects of repeated administration of 3,4-methylenedioxymethamphetamine on 5-hydroxytryptamine neuronal activity and release in the rat brain in vivo

SE Gartside, R McQuade and T Sharp

University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, United Kingdom.

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 raphe 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 raphe nucleus, but a marked reduction in the amount of 5-HT released in the frontal cortex after electrical stimulation of the dorsal raphe 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.

Volume 279, Issue 1, pp. 277-283, 10/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1996 by the American Society for Pharmacology and Experimental Therapeutics.