Transport mechanisms governing serotonin clearance in vivo revealed by high-speed chronoamperometry

Lynette C. Daws, Sylvia Montañez, W. Anthony Owens, Georgianna G. Gould, Alan Frazer, Glenn M. Toney, Greg A. Gerhardt

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

High-speed chronoamperometry was used to determine the kinetics of clearance of exogenously applied serotonin (5-HT) in the dorsal raphe nucleus (DRN), dentate gyrus, CA3 region of the hippocampus or corpus callosum of anesthetized rats. Maximal velocity (Vmax) for 5-HT clearance was greatest in the DRN > dentate gyrus > CA3 > corpus callosum. Apparent affinity (KT) of the serotonin transporter (5-HTT) was similar in DRN and CA3 but greater in dentate gyrus and corpus callosum. A 90% loss of norepinephrine transporters (NET) produced by 6-hydroxydopamine pretreatment, resulted in a two-fold reduction in Vmax and a 30% decrease in K T in the dentate gyrus, but no change in kinetic parameters in the CA3 region. Pretreatment with 5,7-dihydroxytryptamine that resulted in a 90% reduction in 5-HTT density, modestly reduced Vmax in dentate gyrus but not in CA3. The same treatment had no effect on KT in the dentate gyrus but increased KT two-fold in the CA3. Neurotoxin treatments had no effect on 5-HT clearance in the corpus callosum. In hippocampal regions of intact rats, local application of the selective serotonin reuptake inhibitor, fluvoxamine, inhibited 5-HT clearance most robustly when the extracellular concentration of 5-HT was less than the KT value. By contrast, the NET antagonist, desipramine, significantly inhibited 5-HT clearance when extracellular concentrations of 5-HT were greater than the KT value. These data indicate that hippocampal uptake of 5-HT may be mediated by two processes, one with high affinity but low capacity (i.e. the 5-HTT) and the other with low affinity but a high capacity (i.e. the NET). These data show for the first time in the whole animal that 5-HT clearance in brain is regionally distinct with regard to rate and affinity.

Original languageEnglish (US)
Pages (from-to)49-62
Number of pages14
JournalJournal of Neuroscience Methods
Volume143
Issue number1
DOIs
StatePublished - Apr 15 2005

Keywords

  • Chronoamperometry
  • Dorsal raphe nucleus
  • Hippocampus
  • Norepinephrine transporter
  • Rat
  • Serotonin clearance rates
  • Serotonin transporter

ASJC Scopus subject areas

  • Neuroscience(all)

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