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 ac tivity 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 inhibi tor, fluoxetine, and the 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP ), were used to produce an increase in extracellular 5-HT concentratio n. Systemic administration of fluoxetine (10 mg kg(-1), s.c.) produced a 2- to 3-fold increase in extracellular 5-HT concentration but did n ot 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 extr acellular 5-HT concentration in the neostriatum with a slight but non- significant decrease in extracellular dopamine concentration. Pergolid e, a dopamine D-2 agonist, given systemically caused a dramatic decrea se in extracellular dopamine concentration demonstrating the responsiv eness of the neurons. These results demonstrate that high concentratio ns of extracellular 5-HT do not modulate dopamine release in the neost riatum. The possibility that different 5-HT receptor subtypes may medi ate different regulation of dopamine release remains to be explored.