Control of hormonal stress reactivity by the endogenous opioid system
Control of hormonal stress reactivity by the endogenous opioid system
复制标题
DOI：
10.1016/j.psyneuen.2007.12.010
复制
发表时间：
2008-05-01
影响因子：
3.7
通讯作者：
Zimmer, Andreas
中科院分区：
文献类型：
--
作者：
Bilkei-Gorzo, Andras;Racz, Ildiko;Zimmer, Andreas
激素应激反应的调节包括反应的启动、幅度和终止，以及与其他应激反应系统的整合。本研究探讨了内源性阿片类物质在行为，热和激素应激反应的调节和整合中的作用，因为这些神经调节剂及其受体在负责应激反应的边缘结构中表达。为此，我们选择性删除β-内啡肽，脑啡肽或强啡肽的小鼠进行零迷宫测试，轻度应激的情况下，和登记的行为和应激激素水平。采用零迷宫、光暗和惊吓反应范式评估行为应激反应。缺乏脑啡肽的动物在两种模型中的每三种强啡肽敲除中都表现出焦虑相关的行为反应增加，而β-内啡肽敲除的反应表明零迷宫测试中的焦虑水平较低。所有基因敲除菌株均显示激素应激反应性的显著变化。与野生型动物不同，零迷宫测试情况后ACTH水平的增加在Penk 1（-/-）和Pdyn（-/-）小鼠中未能达到显著性水平。皮质酮血浆水平迅速增加，在所有的菌株，具有较低的峰值响应基因敲除。在野生型和β-内啡肽缺乏的小鼠中，皮质酮水平在应激暴露后60分钟内恢复到基线水平。相反，缺乏强啡肽和脑啡肽的小鼠表现出更持久的皮质酮水平升高，表明应激反应延迟终止。重要的是，行为和激素反应在野生型小鼠中相关，但在基因敲除小鼠中不相关。在缺乏强啡肽的动物和Penk 1（-/-）小鼠中，尽管这些品系的行为焦虑水平升高，但由压力引起的体温升高降低。这些结果表明，在整合行为和激素应激反应的内源性阿片系统的重要作用。(C)2008爱思唯尔有限公司保留所有权利。
Regulations of hormonal stress responses entail the initiation, amplitude and termination of the reaction, as well as its integration with other stress response systems. This study investigates the role of endogenous opioids in the regulation and integration of behavioral, thermal and hormonal stress responses, as these neuromodulators and their receptors are expressed in limbic structures responsible for stress responses. For this purpose, we subjected mice with selective deletion of beta-endorphin, enkephatin or dynorphin to the zero-maze test, a mildly stressful situation, and registered behaviors and stress hormone levels. Behavioral stress reactivity was assessed using zero-maze, light-dark and startle-reactivity paradigms. Animals lacking enkephalin displayed increased anxiety-related behavioral responses in each three, dynorphin knockouts in two models, whereas the responses of beta-endorphin knockouts indicated tower anxiety level in the zero-maze test. All knockout strains showed marked changes in hormonal stress reactivity. Increase in ACTH level after zero-maze test situation, unlike in wild type animals, failed to reach the level of significance in Penk1(-/-) and Pdyn(-/-) mice. Corticosterone plasma levels rapidly increased in all strains, with a lower peak response in knockouts. In wild-type and beta-endorphin-deficient mice, corticosterone levels returned to baseline within 60 min after stress exposure. In contrast, mice lacking dynorphin and enkephalin showed longer-lasting elevated corticosterone levels, indicating a delayed termination of the stress reaction. Importantly, the behavioral and hormonal responses correlated in wild-type but not in knockout mice. Hyperthermia elicited by stress was reduced in animals lacking dynorphin and absent in Penk1(-/-) mice, despite of the heightened behavioral anxiety level of these strains. These results demonstrate an important role on the endogenous opioid system in the integration of behavioral and hormonal stress responses. (C) 2008 Elsevier Ltd. All rights reserved.