Effect of paroxetine on extracellular serotonin and dopamine levels in the prefrontal cortex

Abstract.

Paroxetine, a selective serotonin (5-HT) reuptake inhibitor, increased extracellular 5-HT and dopamine levels, as determined by microdialysis, in the medial prefrontal cortex (mPFC) of freely moving rats. There was a difference in the time course of the maximum response between the 5-HT and dopamine levels after paroxetine administration. The extracellular dopamine concentration reached its maximum 20 min after the peak effect of 5-HT had appeared. The paroxetine-induced increase in extracellular dopamine concentration, but not 5-HT concentration, was inhibited by the 5-HT₃-receptor antagonist granisetron. These results suggest that the increase in extracellular dopamine concentration in the mPFC elicited by paroxetine is the result of stimulation of 5-HT₃ receptors by the extracellular accumulation of 5-HT in the mPFC.