Suppression of pro-inflammatory cytokine expression and lack of anti-depressant-like effect of fluoxetine in lipopolysaccharide-treated old female mice

Int Immunopharmacol. 2017 Jul:48:35-42. doi: 10.1016/j.intimp.2017.04.021. Epub 2017 May 3.

Abstract

Some antidepressants show a significantly lower efficacy in elderly patients, particularly in women. Previous studies have shown that antidepressants administered to young animals reduced depression-like symptoms induced by lipopolysaccharide (LPS). The aim of this study was to find out whether the antidepressant and anti-inflammatory properties of fluoxetine (FLU) can be observed also in old female C57BL/6J mice. A depression-like state was evoked by the administration of LPS (100μg/kg for 4 consecutive days) which was followed by reduction of sucrose preference (anhedonia) and enhancement of immobility-time in the forced swim test (FST). Animals, which received FLU (10mg/kg, 11days) exhibited a decreased LPS-induced expression of some inflammatory cytokines in the hippocampus and spleen but this effect was not accompanied by beneficial changes in animals' behavior. Despite the lack of antidepressant-properties of FLU in this model, our studies have proven significant profound anti-inflammatory properties of chronic FLU treatment which may suggest its suitability for fending off inflammatory processes in the elderly.

Keywords: Cytokine; Fluoxetine; Lipopolysaccharide; Old female mice.

MeSH terms

  • Aging / immunology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Cytokines / genetics
  • Cytokines / immunology*
  • Depression / drug therapy
  • Depression / immunology*
  • Female
  • Fluoxetine / pharmacology*
  • Fluoxetine / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / immunology
  • Lipopolysaccharides
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology

Substances

  • Anti-Inflammatory Agents
  • Antidepressive Agents
  • Cytokines
  • Lipopolysaccharides
  • RNA, Messenger
  • Fluoxetine