Quantitative microdialysis of serotonin and norepinephrine: Pharmacological influences on in vivo extraction fraction

The present study was designed to investigate the potential influence of various neuronal processes including uptake, release and metabolism, on the in vivo microdialysis extraction fraction (E(d)) of serotonin (5HT) and norepinephrine (NE). Paroxetine administration decreased the E(d) of 5HT in the nucleus accumbens from 24 +/- 3 to 18 +/- 0.2% (p < 0.05). Similarly, desipramine infusion reduced the NE E(d) from 35 +/- 2 to 26 +/- 1% (p < 0.05). However, perfusion with pargyline or tetrodotoxin had no effect on the E(d) of either 5HT or NE. Perfusion with agonists for the 5HT, alpha-adrenergic, D-2 and histamine receptors had no effect on the E(d) of 5HT. In the same manner, perfusion with the alpha-adrenergic agonists, methoxamine or clonidine, dib not affect the E(d) of NE. These data are in agreement with experimental results obtained for dopamine in the nucleus accumbens and the theory of quantitative microdialysis which predicts that only changes in the rate of clearance will change E(d) of monoamines. These results suggest that, like A, changes in the E(d) for 5HT or NE are indicative of changes in the reuptake of these neurotransmitters. The results also indicate that pharmacological agents which do not affect uptake have no effect on the extraction fraction.