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MDMA induced dopamine release in vivo: role of endogenous serotonin

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Summary

Acting as a substrate at the serotonin (5-HT) transporter, (+)-MDMA (3,4-methylenedioxymethamphetamine), is a potent releaser of 5-HT and causes toxicity to 5-HT neurons after repeated exposure. (+)-MDMA also releases dopamine (DA), although with less potency. Since we have shown previously that the intrastriatal application of 5-HT facilitates DA release, it was hypothesized that increased release of striatal 5-HT after MDMA may influence extracellular levels of DA. Using microdiaiysis in vivo, we found that (+)-MDMA (4.7 μmol/kg, i.v.) administration increased extracellular striatal DA levels to 501% of control (p < 0.01, n=12). However, in the presence of fluoxetine (14.4 μmol/kg, s.c.), which prevents (+)-MDMA effects on 5-HT release, the (+)-MDMA-induced increase in DA was significantly less (to 375% of control, p < 0.05, vs. no fluoxetine, n=8). In vitro studies with striatal slices, to test drug selectivity, showed that (+)-MDMA (0.3-3 μM) increased extracellular levels of both DA and 5-HT in a dose-dependent manner. Fluoxetine (3 μM) completely blocked the effects of (+)-MDMA on 5-HT release, but did not alter (+)-MDMA-induced DA release in vitro. The selective DA transport inhibitor GBR-12909 (1 μM), blocked (+)-MDMA's effect on DA release. It is concluded that 5-HT release after (+)-MDMA treatment partially contributes to (+)-MDMA's effect on DA release in vivo.

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  1. M. P. Galloway

    Present address: Cellular and Clinical Neurobiology, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA

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  1. Cellular and Clinical Neurobiology, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA

    S. Koch

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Koch, S., Galloway, M.P. MDMA induced dopamine release in vivo: role of endogenous serotonin. J. Neural Transmission 104, 135–146 (1997). https://doi.org/10.1007/BF01273176

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