On the in-vivo modulation of neostriatal dopamine release by fluoxetine and 5-hydroxy-L-tryptophan in conscious rats

To help determine the nature of serotonergic regulation of dopamine activity in the brain an in-vivo microdialysis study has been performed in conscious rats to investigate the modulation of dopamine release in the neostriatum by 5-hydroxytryptamine (5-HT). The 5-HT uptake inhibitor, fluoxetine, and the 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP), were used to produce an increase in extracellular 5-HT concentration. Systemic administration of fluoxetine (10 mg kg(-1), s.c.) produced a 2- to 3-fold increase in extracellular 5-HT concentration but did not change extracellular dopamine concentration in the neostriatum. Go-administration of fluoxetine and 5-HTP (40 mg kg(-1), s.c.; 60-90 min after fluoxetine) caused a highly significant tenfold increase in extracellular 5-HT concentration in the neostriatum with a slight but non-significant decrease in extracellular dopamine concentration. Pergolide, a dopamine D-2 agonist, given systemically caused a dramatic decrease in extracellular dopamine concentration demonstrating the responsiveness of the neurons. These results demonstrate that high concentrations of extracellular 5-HT do not modulate dopamine release in the neostriatum. The possibility that different 5-HT receptor subtypes may mediate different regulation of dopamine release remains to be explored.