The aim of the preclinical study was to examine the effects of chronic the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c., once daily, for 14 days) on depression-like behavior following ovariectomy in rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c., once daily, for 14 days). Depression-like behavior was assessed in the forced swimming test (FST) and the spontaneous locomotor activity was assessed using the open field test (OFT). Treatment with cholecalciferol in high dose (5.0 mg/kg/day, s.c.) significantly decreased immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E2 exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose administered alone or together with 17β-E2 significantly enhanced frequency of grooming of the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E2 significantly decreased the elevated corticosterone levels in the blood serum of OVX rats following the FST. These results indicate that cholecalciferol in high dose has a marked antidepressant-like effect in the adult female rats with low levels of estrogen. The data also indicate that the combination of cholecalciferol in high dose and 17β-E2 is more effective than 17β-E2 alone in OVX rats inducing a more profound antidepressant-like effect in the FST.

Russian Science Foundation (RSF) funded the reported study accordingly to the research project № 16-15-10053.