Effects of vortioxetine and fluoxetine on the level of Brain Derived Neurotrophic Factors (BDNF) in the hippocampus of chronic unpredictable mild stress-induced depressive rats

Brain Res Bull. 2018 Sep:142:1-7. doi: 10.1016/j.brainresbull.2018.06.007. Epub 2018 Jun 19.

Abstract

Vortioxetine is a novel antidepressant capable of improving depressive and cognitive symptoms associated with major depressive disorder (MDD). This study established whether treatment with vortioxetine, fluoxetine or vehicle alters the modulation of brain-derived neurotrophic factor (BDNF) under the 21-day chronic unpredictable mild stress (CUMS) condition in 54 Sprague-Dawley rats. Vortioxetine mitigated the reduction in rearing behavior by CUMS in the OFT on day 7 and 21, as well as sucrose preference on day 21. Histological examination by H&E staining showed that most hippocampal neurons in the CUMS + FLU and CUMS + VOR groups were intact, although some of them demonstrated karyopyknosis. The mean optical density value of hippocampal BDNF was significantly higher in the CUMS + VOR group than the CUMS and CUMS + FLU groups. There was a trend towards a higher number of hippocampal BDNF-positive cells in the CUMS + VOR group, although it did not reach statistical significance. In conclusion, vortioxetine, but not fluoxetine, increased hippocampal BDNF levels in rats subject to CUMS.

Keywords: Brain-derived neurotrophic factors; Chronic unpredictable mild stress; Depression; Fluoxetine; Vortioxetine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anhedonia / drug effects
  • Anhedonia / physiology
  • Animals
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / pathology
  • Disease Models, Animal
  • Fluoxetine / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Random Allocation
  • Rats, Sprague-Dawley
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology
  • Vortioxetine / pharmacology*

Substances

  • Antidepressive Agents
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Fluoxetine
  • Vortioxetine