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The purpose of this study was to explore the antidepressant-like effects of vitamin D 3 at different doses (1.0, 2.5, and 5.0 mg/kg sc) on a model of depression produced by chronic unpredictable mild stress (CUMS) for 28 days in long-term (3 months) ovariectomized (OVX) adult rats. Sucrose preference (SPT), forced swimming (FST) and open-field (OFT) tests were conducted to examine the depression-like state. Serum corticosterone/adrenocorticotrophic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3/NT-4 expressions by ELISA kits and/or western blotting were determined to assess the possible mechanisms of the vitamin D 3 effects on the depression-like profile in long-term OVX rats subjected to CUMS. The results showed that vitamin D 3 (5.0 mg/kg), as well as fluoxetine treatment, considerably reversed the depression-like state in the SPT and FST, decreased serum corticosterone/ACTH levels, and increased BDNF and NT-3/NT-4 levels in the hippocampus of long-term OVX rats compared to OVX rats with CUMS ( p &lt; 0.05). Thus, a high dose of vitamin D 3 (5.0 mg/kg sc) could improve the depression-like profile in long-term OVX adult female rats subjected to the CUMS procedure, which might be mediated by the regulation of BDNF and the NT-3/NT-4 signaling pathways in the hippocampus, as well as the corticosterone/ACTH levels of the blood serum.

Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications