Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions
Journal of Neurochemistry – January 01, 1996
Source: OpenAlex
Summary
MDMA significantly boosts serotonin levels, with a dose-dependent increase in extracellular serotonin (5-HT) observed in the striatum and prefrontal cortex. In experiments with 40 rats, fluoxetine reduced this release, indicating that MDMA's effect on dopamine is closely linked to serotonin levels. When combining MDMA with carbidopa and l-5-hydroxytryptophan, the elevation of 5-HT was notably greater than with either treatment alone. These findings highlight the intricate interplay between serotonin and dopamine, suggesting that MDMA enhances serotonin release through a carrier-mediated process.
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.