Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions

J Neurochem. 1996 Jan;66(1):243-9. doi: 10.1046/j.1471-4159.1996.66010243.x.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Hydroxytryptophan / pharmacology
  • Animals
  • Carbidopa / pharmacology
  • Carrier Proteins / physiology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Drug Synergism
  • Fluoxetine / pharmacology
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism*
  • Male
  • Membrane Glycoproteins / physiology*
  • Membrane Transport Proteins*
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity
  • Nerve Tissue Proteins*
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism*
  • Serotonin Agents / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins
  • Tetrodotoxin / pharmacology


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Agents
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Slc6a4 protein, rat
  • Fluoxetine
  • Serotonin
  • Tetrodotoxin
  • 5-Hydroxytryptophan
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Carbidopa
  • Dopamine