Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex

Eur J Pharmacol. 1999 Oct 21;383(1):39-48. doi: 10.1016/s0014-2999(99)00636-6.


Endogenous serotonin (5-hydroxytryptamine, 5-HT)-mediated regulation of dopamine release in the rat prefrontal cortex was pharmacologically characterized using in vivo microdialysis. To increase synaptic 5-HT availability, a selective 5-HT uptake inhibitor fluoxetine was applied via the dialysis probe. Local perfusion of fluoxetine (30 and 100 microM) increased dopamine levels in a concentration-dependent manner. The fluoxetine (100 microM)-induced increases in dopamine release were abolished by pretreatment with the 5-HT(1B/1D) receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide] ) (10 and 100 microM). The facilitation of dopamine release was also prevented by selective inactivation of the mRNA encoding 5-HT(6) receptors using antisense oligonucleotides techniques. These findings suggest that not only 5-HT(1B) receptors but also 5-HT(6) receptors are associated with the endogenous 5-HT-mediated facilitation of dopamine release. In other words, 5-HT(6) receptors may play, in part, a significant role in the functional interaction between the dopaminergic and serotonergic neuronal system in the rat prefrontal cortex.

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Fluoxetine / pharmacology
  • Male
  • Microdialysis
  • Oligonucleotides, Antisense / chemical synthesis
  • Oligonucleotides, Antisense / pharmacology
  • Oxadiazoles / pharmacology
  • Piperazines / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Uptake Inhibitors / pharmacology
  • Time Factors


  • Oligonucleotides, Antisense
  • Oxadiazoles
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • serotonin 6 receptor
  • Fluoxetine
  • GR 127935
  • Serotonin
  • Dopamine