The effects of desipramine, fluoxetine, or tianeptine on changes in bulbar BDNF levels induced by chronic social instability stress and inflammation

Pharmacol Rep. 2017 Jun;69(3):520-525. doi: 10.1016/j.pharep.2017.01.004. Epub 2017 Jan 17.

Abstract

Background: Stress is a major predisposing factor in the development of psychiatric disorders and potential source of augmented inflammatory processes in the brain. Increasing body of evidence shows an important role of alterations in the olfactory bulbs (OBs) function in stress-related disorders. The aim of the present study was to investigate the impact of antidepressants on the alterations of brain-derived neurotrophic factor (BDNF) induced by lipopolysaccharide (LPS) in female rats subjected to chronic social instability stress (CSIS).

Methods: 9 weeks old female rats were subjected to CSIS and injected ip once daily with desipramine (10mg/kg), fluoxetine (5mg/kg), or tianeptine (10mg/kg) for 4 weeks. On the last day of the experiment, rats being at the estrus phase of cycle were injected ip with LPS (1mg/kg) or saline.

Results: The BDNF mRNA and protein levels were evaluated in the olfactory bulbs. and the BDNF protein levels were measured in plasma. A single LPS administration in the stressed rats resulted in significant decrease in the bulbar BDNF mRNA, but not in the protein level. Chronic administration of desipramine, fluoxetine, or tianeptine increased the BDNF mRNA expression and protein levels in the LPS-injected stressed rats. There was no effect of the studied antidepressants on the reduction of the plasma BDNF protein level induced by CSIS and LPS.

Conclusions: These results suggest that studied antidepressants were effective in inhibiting the impact of LPS on BDNF expression in the stressed rats what may be significant for beneficial action of this drugs.

Keywords: Antidepressants; BDNF; Chronic social stress; LPS; Olfactory bulbs.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Desipramine / pharmacology*
  • Disease Models, Animal
  • Female
  • Fluoxetine / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Lipopolysaccharides / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / physiopathology
  • Thiazepines / pharmacology*

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Lipopolysaccharides
  • RNA, Messenger
  • Thiazepines
  • Fluoxetine
  • tianeptine
  • Desipramine