ANTIDEPRESSANT-LIKE EFFECT OF SILDENAFIL THROUGH OXYTOCIN-DEPENDENT CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN PHOSPHORYLATION
ANTIDEPRESSANT-LIKE EFFECT OF SILDENAFIL THROUGH OXYTOCIN-DEPENDENT CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN PHOSPHORYLATION
复制标题
DOI：
10.1016/j.neuroscience.2011.11.001
复制
发表时间：
2012-01-03
期刊：
影响因子：
3.3
通讯作者：
Tomizawa, K.
中科院分区：
文献类型：
--
作者：
Matsushita, H.;Matsuzaki, M.;Tomizawa, K.
血浆中催产素（OT）水平在性反应过程中增加，抑郁症患者血浆中催产素水平显著降低。一种治疗性功能障碍的药物，西地那非，增强了垂体后叶的OT的电诱发释放。在这项研究中，我们发现西地那非通过激活OT信号通路具有抗抑郁样作用。应用西地那非减少雄性小鼠抑郁相关行为。抗抑郁样作用被OT受体（OTR）拮抗剂阻断，并且在OTR敲除（KO）小鼠中不存在。西地那非增加了海马cAMP反应元件结合蛋白（CREB）的磷酸化。OTR拮抗剂抑制西地那非诱导的CREB磷酸化，而西地那非对OTR KO小鼠的CREB磷酸化没有影响。这些结果表明西地那非通过激活OT信号具有抗抑郁样作用，并且是治疗抑郁症的有希望的药物。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Oxytocin (OT) levels in plasma increase during sexual response and are significantly lower in patients with depression. A drug for the treatment of sexual dysfunction, sildenafil, enhances the electrically evoked release of OT from the posterior pituitary. In this study, we showed that sildenafil had an antidepressant-like effect through activation of an OT signaling pathway. Application of sildenafil reduced depression-related behavior in male mice. The antidepressant-like effect was blocked by an OT receptor (OTR) antagonist and was absent in OTR knockout (KO) mice. Sildenafil increased the phosphorylation of cAMP response element-binding protein (CREB) in the hippocampus. The OTR antagonist inhibited sildenafil-induced CREB phosphorylation and sildenafil had no effect on CREB phosphorylation in OTR KO mice. These results suggest sildenafil to have an antidepressant-like effect through the activation of OT signaling and to be a promising drug for the treatment of depression. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.