On the In-vivo Modulation of Neostriatal Dopamine Release by Fluoxetine and 5−Hydroxy-L-tryptophan in Conscious Rats

Publisher Website
Google Scholar
Abstract
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. Co-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 D2 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.

This publication has 16 references indexed in Scilit: