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.
Luthman
J
J
Department of Biochemistry, Preclinical R&D, Astra Arcus AB, Södertälje, Sweden.
Friedemann
M N
MN
Hoffer
B J
BJ
Gerhardt
G A
GA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004563:Electrochemistry; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism; D015031:Zimeldine / Q000494:pharmacology
D015306:Biogenic Monoamines; D005473:Fluoxetine; D016627:Oxidopamine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine