Serotonin (5-HT) transporter (SERT) function after graded destruction of serotonergic neurons

Sylvia Montañez, Lynette C. Daws, Georgianna G. Gould, Alan Frazer

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The degree of occupancy of the serotonin transporter (SERT) by selective serotonin reuptake inhibitors (SSRIs) appears to be critical in determining therapeutic response. To gain insight into the extent of occupancy required to alter serotonergic neurotransmission we used high-speed chronoamperometry to determine the extent of serotonergic destruction required to reduce the clearance of exogenously administered serotonin from extracellular fluid in the CA3 region of the hippocampus. Rats were pretreated with various doses of 5,7-dihydroxytryptamine to produce either a low, intermediate or high loss of SERTs. Clearance of 5-HT was reduced only in rats with > 90% loss of SERT. In these rats, there was also a trend for peak signal amplitudes to be greater. There was no significant difference in these parameters between the sham group and those with low or intermediate loss of SERTs. The SSRI, fluvoxamine, prolonged clearance of 5-HT in sham, low and intermediate groups, whereas there was no effect of fluvoxamine in those rats with > 90% loss of SERT. Functional loss of SERT activity occurs when destruction of serotonergic innervation is greater than 90% but serotonin clearance and efficacy of fluvoxamine is maintained with as few as one fifth of a full complement of SERTs.

Original languageEnglish (US)
Pages (from-to)861-867
Number of pages7
JournalJournal of neurochemistry
Volume87
Issue number4
DOIs
Publication statusPublished - Nov 1 2003

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Keywords

  • 5
  • 7-DHT
  • CA3 region of hippocampus
  • Chronoamperometry
  • Degeneration
  • Rat
  • Serotonin transporter

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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