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. 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.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
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Li
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Perry
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Fuller
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D006916:5-Hydroxytryptophan; D004298:Dopamine; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors