Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia; Laboratory of Comparative Somnology and Neuroendocrinology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia; International Research Centre «Biotechnologies of the Third Millennium», ITMO University, St. Petersburg, Russia.
Department of Obstetrics and Gynecology named after S.N. Davydov, North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia.
Biomed Pharmacother. 2016 Dec;84:1865-1872. doi: 10.1016/j.biopha.2016.10.107. Epub 2016 Nov 12.
Vitamine D (VD) has important functions in the human brain and may play a role in affective-related disorders. VD receptors are expressed in multiple brain regions associated with depressive disorders. The aim of the preclinical study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0mg/kg/day,s.c., once daily, for 14days) on the depression-like behavior and corticosterone levels in the blood samples following ovariectomy in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E, 0.5μg/rat,s.c., once daily, for 14days). Depression-like behavior and spontaneous locomotor activity were assessed in the forced swimming test (FST) and the open field test (OFT), respectively. The corticosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with cholecalciferol in high dose (5.0mg/kg/day,s.c.) significantly decreased the immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose (5.0mg/kg/day,s.c.) administered alone or together with 17β-E significantly enhanced frequency of grooming for the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E 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.
维生素 D(VD)在人类大脑中具有重要功能,可能在情感相关障碍中发挥作用。VD 受体在与抑郁障碍相关的多个脑区表达。这项临床前研究的目的是检查慢性胆钙化醇给药(1.0、2.5 或 5.0mg/kg/天,皮下注射,每天一次,共 14 天)对去卵巢雌性大鼠抑郁样行为和血液样本中皮质酮水平的影响。胆钙化醇给予去卵巢(OVX)大鼠和用 17β-雌二醇(17β-E,0.5μg/大鼠,皮下注射,每天一次,共 14 天)治疗的 OVX 大鼠。在强迫游泳试验(FST)中评估抑郁样行为,在旷场试验(OFT)中评估自发运动活动。所有实验组均在 FST 前后测量血清皮质酮水平。高剂量(5.0mg/kg/天,皮下注射)胆钙化醇治疗显着降低了 FST 中 OVX 大鼠的不动时间。高剂量胆钙化醇与 17β-E 联合给药对相同的抑郁样行为测试模型中的 OVX 大鼠表现出明显的协同抗抑郁作用。高剂量(5.0mg/kg/天,皮下注射)胆钙化醇单独或与 17β-E 联合给药显着增加了 OVX 大鼠在 OFT 中的梳理频率。此外,高剂量胆钙化醇单独或与 17β-E 联合给药显着降低了 FST 后 OVX 大鼠血液中皮质酮水平的升高。这些结果表明,高剂量胆钙化醇在雌激素水平低的成年雌性大鼠中具有明显的抗抑郁样作用。