In conclusion, this study evidences the anti-anhedonia-like and antidepressant-like effects of the repeated administration of VD3 in a chronic stress model of depression and the biochemical and western blotting assays confirm the implications of BDNF/NT-3/NT-4 modulation in the antidepressant-like activity of VD3 in long-term OVX adult rats with CUMS. This evidence concerns the gene BDNF and major depressive disorder.