MDMA induced dopamine release in vivo: role of endogenous serotonin
| Autor: | M. P. Galloway, S. Koch |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Serotonin Microdialysis Dopamine N-Methyl-3 4-methylenedioxyamphetamine In Vitro Techniques Pharmacology Piperazines Rats Sprague-Dawley chemistry.chemical_compound Serotonin Agents Dopamine Uptake Inhibitors In vivo Fluoxetine mental disorders medicine Extracellular Animals Neurotransmitter Chromatography High Pressure Liquid Biological Psychiatry Transport inhibitor Rats Neostriatum Psychiatry and Mental health Neurology chemistry Catecholamine Ketanserin Serotonin Antagonists Neurology (clinical) Selective Serotonin Reuptake Inhibitors psychological phenomena and processes medicine.drug |
| Zdroj: | Journal of Neural Transmission. 104:135-146 |
| ISSN: | 1435-1463 0300-9564 |
| DOI: | 10.1007/bf01273176 |
| Popis: | 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 facilities DA release, it was hypothesized that increased release of striatal 5-HT after MDMA may influence extracellular levels of DA. Using microdialysis in vivo, we found that (+)-MDMA (4.7 mumol/kg, i.v.) administration increased extracellular striatal DA levels to 501% of control (p0.01, n = 12). However, in the presence of fluoxetine (14.4 mumol/kg, s.c.), which prevents (+)-MDMA effects on 5-HT release, the (+)-MDMA-induced increase in DA was significantly less (to 375% of control, p0.05, vs. no fluoxetine, n = 8). In vitro studies with striatal slices, to test drug selectivity, showed that (+)-MDMA (0.3-3 microM) increased extracellular levels of both DA and 5-HT in a dose-dependent manner. Fluoxetine (3 microM) 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 microM), 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. |
| Databáze: | OpenAIRE |
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