Corelease of dopamine and serotonin from striatal dopamine terminals

Neuron. 2005 Apr 7;46(1):65-74. doi: 10.1016/j.neuron.2005.02.010.


The striatum receives rich dopaminergic and more moderate serotonergic innervation. After vesicular release, dopamine and serotonin (5-hydroxytryptamine, 5-HT) signaling is controlled by transporter-mediated reuptake. Dopamine is taken up by dopamine transporters (DATs), which are expressed at the highest density in the striatum. Although DATs also display a low affinity for 5-HT, that neurotransmitter is normally efficiently taken up by the 5-HT transporters. We found that when extracellular 5-HT is elevated by exogenous application or by using antidepressants (e.g., fluoxetine) to inhibit the 5-HT transporters, the extremely dense striatal DATs uptake 5-HT into dopamine terminals. Immunohistochemical results and measurements using fast cyclic voltammetry showed that elevated 5-HT is taken up by DATs into striatal dopamine terminals that subsequently release 5-HT and dopamine together. These results suggest that antidepressants that block serotonin transporters or other factors that elevate extracellular 5-HT alter the temporal and spatial relationship between dopamine and 5-HT signaling in the striatum.

Publication types

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

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / analysis
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Fluoxetine / pharmacology
  • Immunohistochemistry
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Serotonin / analysis
  • Serotonin / metabolism*


  • Antidepressive Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Fluoxetine
  • Serotonin
  • Dopamine