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

• Published in: Biological psychiatry (1969) 2007-01, Vol.61 (2), p.210-215
• Main Authors: Gould, Georgianna G, Javors, Martin A, Frazer, Alan
• Format: Article
• Language: English
• Subjects: Adrenergic Uptake Inhibitors - pharmacology; Animals; Antidepressive Agents - pharmacology; Autoradiography; Biological and medical sciences; Brain - drug effects; Chromatography, High Pressure Liquid; Desipramine - pharmacology; Dose-Response Relationship, Drug; Duloxetine Hydrochloride; Male; Medical sciences; Neuropharmacology; Norepinephrine Plasma Membrane Transport Proteins - drug effects; Paroxetine - pharmacology; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-1 - drug effects; Serotonin Plasma Membrane Transport Proteins - drug effects; Serotonin Uptake Inhibitors - pharmacology; Thiophenes - pharmacology
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.02.029

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 [3 H] cyanoimipramine binding to serotonin transporters, but only desipramine treatment significantly reduced [3 H] 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.