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

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Summary

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.

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  1. J. Luthman

    Present address: Department of Biochemistry, Preclinical R&D, Astra Arcus AB, Södertälje, Sweden

Authors and Affiliations

  1. Departments of Psychiatry, Pharmacology and Neuroscience Training Program and Rocky Mountain Center for Sensor Technology, University of Colorado Health Sciences Center, Denver, CO, USA

    M. N. Friedemann, B. J. Hoffer & G. A. Gerhardt

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  1. J. Luthman
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  3. B. J. Hoffer
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  4. G. A. Gerhardt
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Luthman, J., Friedemann, M.N., Hoffer, B.J. et al. In vivo electrochemical measurements of serotonin clearance in rat striatum: effects of neonatal 6-hydroxydopamine-induced serotonin hyperinnervation and serotonin uptake inhibitors. J. Neural Transmission 104, 379–397 (1997). https://doi.org/10.1007/BF01277658

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