Effect of Chronic Administration of Duloxetine on Serotonin and Norepinephrine Transporter Binding Sites in Rat Brain

Georgianna G Gould, Martin A Javors, Alan Frazer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Chronic treatment of rats with certain selective serotonin or norepinephrine reuptake inhibitors produces significant decreases, respectively, in serotonin and norepinephrine transporter binding sites in brain. Duloxetine may be a dual serotonin/norepinephrine reuptake inhibitor, as it is only a slightly more potent inhibitor of serotonin than norepinephrine uptake in vitro. Consequently, we hypothesized that chronic duloxetine treatment, at doses producing serum levels within its therapeutic range, would affect both monoamine transporters dose-dependently, with a higher dose causing greater reductions of binding sites for both transporters. Methods: Rats were treated with either 4 or 8 mg/kg/d of duloxetine, paroxetine, desipramine, or vehicle via subcutaneous osmotic minipumps for 21 days. Binding sites for serotonin and norepinephrine transporters were measured in amygdala and hippocampus using quantitative autoradiography. Results: Both doses of duloxetine and paroxetine produced equivalent and significant decreases in [3H] cyanoimipramine binding to serotonin transporters, but only desipramine treatment significantly reduced [3H] nisoxetine binding to norepinephrine transporters. Conclusions: At doses producing rat serum concentrations in the range achieved in patients at recommended daily doses of the drug, duloxetine behaves in vivo more as a selective serotonin reuptake inhibitor than a dual reuptake inhibitor in its capacity to selectively reduce serotonin transporter density.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalBiological Psychiatry
Volume61
Issue number2
DOIs
StatePublished - Jan 15 2007

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Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Binding Sites
Brain
Paroxetine
nisoxetine
Desipramine
Serotonin Uptake Inhibitors
Therapeutics
Amygdala
Autoradiography
Serum
Hippocampus
Duloxetine Hydrochloride
Pharmaceutical Preparations
Serotonin and Noradrenaline Reuptake Inhibitors

Keywords

  • Autoradiography
  • binding
  • dual uptake inhibitor
  • duloxetine
  • norepinephrine transporter
  • serotonin transporter

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Effect of Chronic Administration of Duloxetine on Serotonin and Norepinephrine Transporter Binding Sites in Rat Brain. / Gould, Georgianna G; Javors, Martin A; Frazer, Alan.

In: Biological Psychiatry, Vol. 61, No. 2, 15.01.2007, p. 210-215.

Research output: Contribution to journalArticle

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