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

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.