**Abstract**

The aim of the present study was to focus on the effects of Vitamin D3 (VD3) supplementation (5.0 mg/kg, s.c.) on the NF-kB/p65, 17β-estradiol (17β-E2)/ VD3 receptors expression in the hippocampus in the long-term ovariectomized (OVX) rats treated with low dose of 17β-E2 (0.5 μg/rat, s.c.) submitted for the chronic unpredictable mild stress (CUMS) for 28 days. Sucrose preference (SPT), forced swimming (FST), and open-field (OFT) tests were conducted to estimate the anhedonia-/depression-like states. NF-kB/p65, 17β-E2/VD3 receptors levels in the hippocampus were evaluated by ELISA and Western blot assays. The findings demonstrated that VD3 at high dose (5.0 mg/kg, s.c.) in a combination with low dose of 17β-E2 decreased anhedonia in the SPT and depression-like behavior in the FST of the long-term OVX rats submitted to CUMS. VD3 (5.0 mg/kg) resulted in significant decreased levels of hippocampal NF-kB/p65 protein expression, as well as to the normalization of hippocampal 17β-E2/VD3 receptors levels in long-term OVX rats treated with 17β-E2 exposed to CUMS. In conclusion, VD3 (5.0 mg/kg, s.c.) in a combination with low dose of 17β-E2 had a synergic antianhedonic- and antidepressant-like effects in the adult female rats following long-term ovariectomy submitted to CUMS.

**Keywords:** vitamin D3, long-term ovariectomy, chronic unpredictable mild stress, NF-kB/p65, 17β-estradiol receptor, vitamin D3 receptors
