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.
Highlights
The global population of menopausal women is on the rise and expected to increase from 470 million in 1990 to 1.2 billion by the year 2030 [1]
The intact rats treated with diazepam (1.0 mg/kg IP) demonstrated a significant increase of the rats treated with cholecalciferol at a doses of 1.0 mg/kg and 2.5 mg/kg showed no modification in time spent into the open arms as compared to the control rats (Figure 1a, p < 0.05)
The intact rats treated with cholecalciferol at a doses of 1.0 mg/kg and 2.5 mg/kg showed no modification in the treated with cholecalciferol at a dose of 5.0 mg/kg showed a significant increase in the time spent in time spent in the open arms as compared to the control rats (Figure 1a, p > 0.05)
Summary
The global population of menopausal women is on the rise and expected to increase from 470 million in 1990 to 1.2 billion by the year 2030 [1]. Hormone replacement therapy has been widely available and used to ameliorate physiological and behavioral alterations in the postmenopausal women [5]. While hormone replacement therapy is accepted as the gold standard for estrogen replacement during menopause, alternative and additional treatments that are more effective are continuously being sought [6]. Considering the wide use of complementary and alternative medications such as vitamin supplements in menopausal patients and our insufficient knowledge about the interaction between hormone. Vitamin D (VD) could be one such candidate substance as additional supplementation for treatment of anxiety-related disorders in women with an imbalance of estrogens. In addition to its classic role in bone metabolism, VD may have many potential non-skeletal functions [10,11,12]. The hormonal functions of vitamin D are mediated through the vitamin D receptor (VDR), a member of the nuclear receptors superfamily of ligand-activated transcriptor factors [11,12,13]
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