Repeated swim stress induces kappa opioid-mediated activation of extracellular signal-regulated kinase 1/2.
Repeated swim stress induces kappa opioid-mediated activation of extracellular signal-regulated kinase 1/2.
复制标题
重复的游泳应力诱导阿片类阿片类药物介导的细胞外信号调节激酶1/2的激活。
DOI：
10.1097/wnr.0b013e32830dd655
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发表时间：
2008-09-17
期刊：
影响因子：
1.7
通讯作者：
Chavkin C
中科院分区：
文献类型：
--
作者：
Bruchas MR;Xu M;Chavkin C
以往的研究表明，强啡肽-κ阿片受体（KOR）系统作为一个关键的调解人的烦躁不安引起的厌恶反复应激暴露后，但分子信号转导机制没有得到充分的表征。在这项研究中，我们报告说，反复强迫游泳应激引起的ERK 1/2 MAPK的显着磷酸化的尾状核和纹状体区的小鼠。激活被KOR拮抗剂norbinaltorphimine阻断，并且在KOR敲除小鼠中不存在。与应激诱导的强啡肽释放激活p38-MAPK相反，KOR介导的ERK 1/2磷酸化不依赖于G蛋白偶联受体激酶3的表达。这些结果表明，应激诱导的强啡肽-KOR系统激活ERK 1/2 MAPK信号通路，这可能有助于重复应激暴露的行为反应。
Previous studies identified the dynorphin-kappa opioid receptor (KOR) system as a critical mediator of dysphoria-induced aversion following repeated stress exposure, but the molecular signaling mechanisms were not fully characterized. In this study we report that repeated forced swim-stress caused a significant phosphorylation of ERK1/2 MAPK in both the caudate and nucleus accumbens regions of the mouse striatum. Activation was blocked by the KOR antagonist, norbinaltorphimine, and absent in KOR knockout mice. In contrast to p38-MAPK activation by stress-induced dynorphin release, KOR-mediated ERK1/2 phosphorylation was not dependent on G-protein coupled receptor kinase 3 expression. These results indicate stress-induced activation of the dynorphin-KOR systems activates ERK1/2 MAPK signaling, and this may contribute to the behavioral responses to repeated stress exposure.