Carrier-Mediated Release of Serotonin by 3,4-Methylenedioxymethamphetamine: Implications for Serotonin-Dopamine Interactions |
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Authors: | Gary A. Gudelsky J. Frank Nash |
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Affiliation: | Departments of Psychiatry and Pharmacology, Case Western Reserve University, Cleveland;and; Proctor and Gamble Co., Cincinnati, Ohio, U.S.A. |
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Abstract: | Abstract: In vivo microdialysis was used to determine whether the 3,4-methylenedioxymethamphetamine (MDMA)-induced release of serotonin (5-HT) in vivo involves a carrier-mediated process and to investigate further the state-dependent interaction between 5-HT and dopamine. MDMA produced a dose-dependent increase in the extracellular concentration of 5-HT in the striatum and prefrontal cortex that was attenuated by treatment with fluoxetine but not by tetrodotoxin. Suppression by fluoxetine of the MDMA-induced release of 5-HT was accompanied by a suppression of the MDMA-induced release of dopamine. Administration of MDMA to rats treated with carbidopa and l -5-hydroxytryptophan resulted in a synergistic elevation of the extracellular concentration of 5-HT that was much greater than that produced by either treatment alone. The MDMA-induced release of dopamine by MDMA also was potentiated in 5-hydroxytryptophan-treated rats. These data are consistent with the view that MDMA increases the extracellular concentration of 5-HT by facilitating carrier-mediated 5-HT release, which can be enhanced greatly under conditions in which 5-HT synthesis is stimulated. Moreover, these data are supportive of a state-dependent, stimulatory role of 5-HT in the regulation of dopamine release. |
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Keywords: | 3,4-Methylenedioxymethamphetamine Dopamine Serotonin |
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