A role for corticotropin releasing factor and urocortin in behavioral responses to stressors
A role for corticotropin releasing factor and urocortin in behavioral responses to stressors
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DOI：
10.1016/s0006-8993(99)01991-5
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发表时间：
1999-11-27
期刊：
影响因子：
2.9
通讯作者：
Heinrichs, SC
中科院分区：
文献类型：
--
作者：
Koob, GF;Heinrichs, SC
促肾上腺皮质激素释放因子（Corticotropin-releasing factor，CRF）及其相关神经肽在中枢神经系统介导应激性行为反应中具有重要作用，CRF受体拮抗剂能有效逆转应激性行为抑制和激活。已在大脑中发现了另一种类似CRF的神经肽尿皮质素，除了对CRF-1受体外，还对CRF-2受体具有高亲和力。Urocortin具有CRF的许多作用，但在禁食和自由进食大鼠中减少进食方面也比CRF更有效。在小鼠遗传模型中，与野生型小鼠相比，过表达CRF的小鼠显示出致焦虑样反应，与野生型小鼠相比，缺乏CRF-1受体的小鼠显示出抗焦虑样行为特征。迄今为止的结果导致了这样的假设，即CRF-1受体可能介导CRF样神经肽对应激源的行为反应的作用，但CRF-2受体可能介导CRF样神经肽产生的摄食抑制。CRF的行为效应的脑部位包括蓝斑（LC）、下丘脑室旁核（PVN）、终纹床核（BNST）和杏仁核中央核。在急性戒断所有主要滥用药物的过程中，CRF也可能被激活，最近的数据表明，CRF可能促成与长期服用滥用药物有关的依赖性和易复发性。这些数据表明，CRF系统在大脑中有一个独特的作用，在调解行为反应，以不同的压力。这些系统可能是特别重要的情况下，一个有机体必须动员不仅垂体肾上腺系统，但也中枢神经系统，以应对环境的挑战。显然，这种基本的大脑激活系统的功能障碍可能是各种病理生理学状况的关键，这些病理生理学状况涉及对压力源的异常反应，如焦虑症、情感障碍和神经性厌食症。(C)1999 Elsevier Science B. V.保留所有权利。
Corticotropin-releasing factor (CRF) and CRF-related neuropeptides have an important role in the central nervous system to mediate behavioral responses to stressors, CRF receptor antagonists are very effective in reversing stress-induced suppression and activation in behavior. An additional CRF-like neuropeptide, urocortin, has been identified in the brain and has a high affinity for the CRF-2 receptor in addition to the CRF-1 receptor. Urocortin has many of the effects of CRF but also is significantly more potent than CRF in decreasing feeding in both meal-deprived and free-feeding rats. In mouse genetic models, mice over-expressing CRF show anxiogenic-like responses compared to wild-type mice, and mice lacking the CRF-1 receptor showed an anxiolytic-like behavioral profile compared to wild-type mice. Results to date have led to the hypothesis that CRF-1 receptors may mediate CRF-like neuropeptide effects on behavioral responses to stressors, but CRF-2 receptors may mediate the suppression of feeding produced by CRF-Like neuropeptides. Brain sites for the behavioral effects of CRF include the locus coeruleus (LC), paraventricular nucleus (PVN) of the hypothalamus, the bed nucleus of the stria terminalis (BNST), and the central nucleus of the amygdala. CRF may also be activated during acute withdrawal from all major drugs of abuse, and recent data suggest that CRF may contribute to the dependence and vulnerability to relapse associated with chronic administration of drugs of abuse. These data suggest that CRF systems in the brain have a unique role in mediating behavioral responses to diverse stressors. These systems may be particularly important in situations were an organism must mobilize not only the pituitary adrenal system, but also the central nervous system in response to environmental challenge. Clearly, dysfunction in such a fundamental brain-activating system may be the key to a variety of pathophysiological conditions involving abnormal responses to stressors such as anxiety disorders, affective disorders, and anorexia nervosa. (C) 1999 Elsevier Science B.V. All rights reserved.