In vivo electrochemical measurements of serotonin clearance in rat striatum: effects of neonatal 6-hydroxydopamine-induced serotonin hyperinnervation and serotonin uptake inhibitors

Diffusion and clearance of extracellular serotonin (5-HT) was examined using in vivo chronoamperometry with ''delayed-pulse'' recordings after pressure ejections of 1 to 60 picomoles 5-HT into rat striatum at a fixed distance from a Nafion-coated carbon fiber electrode. Signals obtained were identified based on the signal characteristics to consist of 5-HT. Clearance times of 5-HT decreased, while amplitudes and rise times increased with serotonergic hyperinnervation induced by neonatal 6-hydroxydopamine (6-OHDA) lesions of dopamine (DA) neurons. Local applications of the 5-HT uptake inhibitors zimelidine or fluoxetine, in conjunction with 5-HT ejections, produced increased clearance times in both normal and 6-OHDA-treated animals. Thus, direct in vivo evidence was obtained for the importance of high affinity nerve terminal uptake as a key mechanism for clearance of 5-HT from the extracellular space. Inhibitors of 5-HT uptake appear to prolong the extracellular presence of 5-HT by increasing its clearance time.