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

Denis BARANENKO1, Julia FEDOTOVA1, 2, *, Annemieke Johanna Maria VAN DEN TOL3

1 International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, 9 Lomonosova Str. St. Petersburg, 191002, Russia
2 Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology RASci., 6 Emb. Makarova, St. Petersburg, 199034, Russia
3 University of Lincoln, School of Psychology Sarah Swift Building 3201, Brayford Pool, Lincoln, LN5 7AY, UK.

* Address correspondence to: Julia Fedotova,

BIOCELL 2019, 43(4), 299-311.


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 longterm 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.


Cite This Article

BARANENKO, D., FEDOTOVA, J., Johanna, A. (2019). Vitamin D3 attenuates anxiety-like behavior in long-term ovariectomized rats with unpredictable mild stress. BIOCELL, 43(4), 299–311.

This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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