EFFECTS OF REPEATED ADMINISTRATION OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE ON 5-HYDROXYTRYPTAMINE NEURONAL-ACTIVITY AND RELEASE IN THE RAT-BRAIN IN-VIVO

In experimental animals, administration of 3,4-methylenedioxymethamphe tamine (MDMA, Ecstasy) leads to extensive, but incomplete, loss of 5-h ydroxytryptamine (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 aft er 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 nuc leus; 2) no change in basal extracellular 5-HT in either the frontal c ortex or the hippocampus, although extracellular 5-hydroxyindoleacetic acid was reduced by about 50% in both regions; and 3) no change in th e amount of 5-HT released in the hippocampus in response to electrical stimulation (5 Hz) of either the dorsal or median raphe nucleus, but a marked reduction in the amount of 5-HT released in the frontal corte x after electrical stimulation of the dorsal raphe nucleus. In summary , although MDMA causes marked 5-HT neurotoxicity, our data suggest tha t 5-HT cell firing is unchanged and, furthermore, that 5-HT release is maintained in some (but not all) forebrain regions even in response t o physiological levels of stimulation.