Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Division of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
Neuropsychopharmacol Rep. 2022 Sep;42(3):356-361. doi: 10.1002/npr2.12271. Epub 2022 Jun 21.
Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant-like effects in male rodents. However, depression is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant-like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)-induced depression.
Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety- and depression-like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants.
Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p-CREB and BDNF in the hippocampus.
OT may exert antidepressant-like effects by activating hippocampal CREB-BDNF signaling in a female mouse model of depression.
慢性应激和糖皮质激素暴露是抑郁的危险因素。催产素 (OT) 已被证明对雄性啮齿动物具有抗应激和抗抑郁样作用。然而,女性患抑郁症的比例是男性的两倍,目前尚不清楚 OT 是否对患有抑郁症的女性具有抗抑郁样作用。因此,在这项研究中,我们研究了慢性 OT 给药在地塞米松 (DEX) 诱导的雌性小鼠抑郁模型中的治疗效果。
雌性 C57BL/6J 小鼠每天接受生理盐水(载体,皮下注射)、DEX(皮下注射)或 OT(腹腔注射)+DEX(皮下注射)治疗 8 周,然后评估焦虑和抑郁样行为。我们还检查了海马体中磷酸化 cAMP 反应元件结合蛋白 (p-CREB) 和脑源性神经营养因子 (BDNF) 的水平,这是对抗抑郁药反应的重要介质。
同时给予 OT 治疗可阻断 DEX 对情绪行为的不利影响。此外,它还上调了海马体中的 p-CREB 和 BDNF。
OT 可能通过激活抑郁模型中小鼠海马体中的 CREB-BDNF 信号通路发挥抗抑郁样作用。