Release and metabolism of 5-hydroxytryptamine in the cat spinal cord examined with microdialysis

L. S. Sorkin, M. G. Hughes, D. Liu, W. D. Willis, D. J. McAdoo

Research output: Contribution to journalArticle

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Abstract

The primary objective of this work was to investigate how in vivo administration of depolarizing agents increases extracellular concentrations of 5-hydroxytryptamine (5-HT) and simultaneously decreases levels of its chief metabolite 5-hydroxyindole-3-acetic acid (5-HIAA). To this end the effects of a number of agents on extracellular levels of 5-HT and 5-HIAA in cat spinal cord were determined by microdialysis and high-pressure liquid chromatography with electrochemical detection. The semipermeable portion of the dialysis probe was centered in the dorsal horn. Artificial cerebrospinal fluid containing elevated K+ or drugs was introduced into the dorsal horn via the dialysis probe. Increases in recovered 5-HT were assumed to reflect increased levels in the extracellular fluid due to release, reduced reuptake and/or reduced metabolism. Depolarizing agents (K+, veratridine and aconitine) increased 5-HT, but dramatically decreased 5-HIAA levels. Extracellular 5-HT returned to near base-line levels with removal of the depolarizing agents. The reduction in 5-HIAA was transient after potassium infusion, but outlasted the infusion of veratridine or aconitine by several hours. Reduction of 5-HIAA could be blocked or reversed with the Na+ channel blockers, lidocaine and tetrodotoxin. Evidently, the decrease in 5-HT metabolism followed activation of sodium channels. Parachloroamphetamine caused an increase in 5-HT levels, presumably reflecting increased 5-HT release, but did not change 5-HIAA levels. Although fluoxetine increased 5-HT, it reduced 5-HIAA, presumably through blockade of 5-HT reuptake leading to a secondary reduction in metabolism. The monoamine oxidase (MAO) inhibitors, pargyline and clorgyline, also caused increases in 5-HT and reductions in 5-HIAA, results expected from inhibition of MAO. Prior administration of fluoxetine or MAO inhibitors did not prevent the decrease in 5-HIAA caused by depolarizing agents. The changes in 5-HT and 5-HIAA produced by local application of depolarizing agents were attributed to release of 5-HT and and independent reduction in its metabolism.

Original languageEnglish (US)
Pages (from-to)192-199
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume257
Issue number1
StatePublished - 1991

Fingerprint

Microdialysis
Serotonin
Spinal Cord
Cats
Acetic Acid
Aconitine
Veratridine
Monoamine Oxidase Inhibitors
Fluoxetine
Dialysis
p-Chloroamphetamine
Clorgyline
5-hydroxyindole
Pargyline
Sodium Channels
Extracellular Fluid
Monoamine Oxidase
Tetrodotoxin
Lidocaine
Cerebrospinal Fluid

ASJC Scopus subject areas

  • Pharmacology

Cite this

Release and metabolism of 5-hydroxytryptamine in the cat spinal cord examined with microdialysis. / Sorkin, L. S.; Hughes, M. G.; Liu, D.; Willis, W. D.; McAdoo, D. J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 257, No. 1, 1991, p. 192-199.

Research output: Contribution to journalArticle

Sorkin, L. S. ; Hughes, M. G. ; Liu, D. ; Willis, W. D. ; McAdoo, D. J. / Release and metabolism of 5-hydroxytryptamine in the cat spinal cord examined with microdialysis. In: Journal of Pharmacology and Experimental Therapeutics. 1991 ; Vol. 257, No. 1. pp. 192-199.
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