Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice

Sylvia Montañez, W. Anthony Owens, Georgianna G. Gould, Dennis L. Murphy, Lynette C. Daws

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Clearance rates for serotonin (5-HT) in heterozygote (+/-) and homozygote (-/-) serotonin transporter (5-HTT) knockout (KO) mice have not been determined in vivo. Moreover, the effect of selective serotonin reuptake inhibitors (SSRIs) on 5-HT clearance in these mice has not been examined. In this study, the rate of clearance of exogenously applied 5-HT was measured in the CA3 region of the hippocampus of anesthetized mice using high-speed chronoamperometry. Compared with wild-type mice, the maximal rate of 5-HT clearance from extracellular fluid (ECF) was decreased in heterozygotes and more markedly so in KO mice. Heterozygote mice were more sensitive to the 5-HT uptake inhibitor, fluvoxamine, resulting in longer clearance times for 5-HT than in wild-type mice; as expected, the KO mice were completely unresponsive to fluvoxamine. There were no associated changes in norepinephrine transporter density, nor was there an effect of the norepinephrine uptake inhibitor, desipramine, on 5-HT clearance in any genotype. Thus, adaptive changes in the norepinephrine transport system do not occur in the CA3 region of hippocampus as a consequence of 5-HTT KO. These data highlight the potential of the heterozygote 5-HTT mutant mice to model the dynamic in vivo consequences of the human 5-HTT polymorphism.

Original languageEnglish (US)
Pages (from-to)210-219
Number of pages10
JournalJournal of Neurochemistry
Volume86
Issue number1
DOIs
StatePublished - Jul 1 2003

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Keywords

  • Chronoamperometry
  • Hippocampus
  • Norepinephrine transporter
  • Serotonin clearance rates
  • Serotonin transporter
  • Serotonin transporter knockout mice

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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