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 aft er pressure ejections of 1 to 60 picomoles 5-HT into rat striatum at a fixed distance from a Nafion-coated carbon fiber electrode. Signals o btained 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 neonata l 6-hydroxydopamine (6-OHDA) lesions of dopamine (DA) neurons. Local a pplications of the 5-HT uptake inhibitors zimelidine or fluoxetine, in conjunction with 5-HT ejections, produced increased clearance times i n both normal and 6-OHDA-treated animals. Thus, direct in vivo evidenc e was obtained for the importance of high affinity nerve terminal upta ke as a key mechanism for clearance of 5-HT from the extracellular spa ce. Inhibitors of 5-HT uptake appear to prolong the extracellular pres ence of 5-HT by increasing its clearance time.