Vitamin D3 attenuates anxiety-like behavior in long-term ovariectomized rats with unpredictable mild stress

Abstract

The impact of various vitamin D3 (VD3) doses (1.0, 2.5, or 5 mg/kg, s.c.) in mitigating the negative consequences of chronic unpredictable mild stress (CUMS) was investigated. Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test (SPT), the elevated plus-maze (EPM), the light/dark test (LDT), and the open-field test (OFT) to measure anhedonia-like and anxiety-like behavior. The corticosterone (CS) and adrenocorticotrophic hormone (ACTH) concentrations in blood serum and the brain-derived neurotrophic factor (BDNF) expression in the hippocampus of long-term ovariectomized (OVX) rats were measured by ELISA kits and/ or western blotting. Treatment with VD3 (5.0 mg/kg), similarly to fluoxetine (10.0 mg/kg), significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT, and CS and ACTH levels in blood serum. It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats. Thus, these findings suggest that VD3 (5.0 mg/kg) administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS. This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.