Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy

Abstract

The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2) on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days) on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX) rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light/dark test (LDT), and locomotor and grooming activities were tested in the open field test (OFT). Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency.

Epigallocatechin‐3‐O‐gallate modulates the diversity of gut microbiota in ovariectomized rats

“…In this study, the ovariectomized group rats exhibited anxiety-like behavior as observed through OFT and EPM. This corroborated the findings of Fedotova et al that the anxiety-like state is enhanced in OVX rats compared with normal rats (Fedotova, Pivina, & Sushko, 2017). Meanwhile, OVX rats which were treated with EGCG showed a decreased anxiety-like state compared with untreated OVX rats.…”

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

“…The aim of the present work was to clarify the anxiolyticlike effect of VD 3 at different doses and to further study the role of the BDNF signaling pathway, as well as the HPA axis, on a rat model of CUMS. As in prior research (Fedotova et al, 2017(Fedotova et al, , 2018Fedotova, 2019), we used long-term estrogen deficiency caused by a post-ovariectomy period of 3 months. This animal model is widely utilized in preclinical behavioral research producing a menopausal-like state in women (Bekku and Yoshimura, 2005).…”

“…For the sham operation, the same procedure was followed but without the amputation of the ovaries. This entire procedure was performed in line with previously published research (Fedotova et al, 2017).…”

“…Since, we did not find any differences between these experimental groups, the physiological saline as a solvent for SHAM/OVX females was used in the present work. The doses of VD 3 were based on our previous studies on the behavioral effects of VD 3 on anxiety-like behavior of non-stressed long-term OVX female rats (Fedotova et al, 2017). All tested doses of VD 3 were safe for animals did not induce any side effects (Fedotova et al, 2017).…”

“…Females going through menopause are at higher risk of developing vitamin D (VD) deficiency due to several reasons: a diet low in VD, restricted outdoor activity resulting in less sun exposure, and a decreased capacity to produce enough calcitriol as a result of an age-related decline in *Address correspondence to: Julia Fedotova, julia.fedotova@mail.ru hydroxylation by the kidneys (Gaugris et al, 2005;Kjaergaard et al, 2011). Our previous experiments have confirmed that the hormonal profile in ovariectomized (OVX) female rodents and menopausal women is also characterized by VD deficiency (Fedotova et al, 2017(Fedotova et al, , 2018Fedotova, 2019). Traditional methods of affective-related disorders therapy, which also includes antidepressants/anxiolytics, are unfortunately of limited effectiveness (Arevalo et al, 2015).…”