Corticotropin-releasing factor, norepinephrine, and stress
Corticotropin-releasing factor, norepinephrine, and stress
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DOI：
10.1016/s0006-3223(99)00164-x
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发表时间：
1999-11-01
影响因子：
10.6
通讯作者：
Koob, GF
中科院分区：
文献类型：
--
作者：
Koob, GF
中枢神经系统中的促肾上腺皮质激素释放因子（CRF）及其相关肽似乎具有激活行为的特性，并增强对应激源的行为反应。CRF和urocortin注射到大脑中产生增加的觉醒，如通过运动激活和增加的应激刺激反应所测量的。CRF的这些作用似乎不依赖于垂体肾上腺轴，并且可以被特异性和选择性CRF拮抗剂α-螺旋CRF 9 -41和D-Phe CRF 12 -41逆转。也许更重要的是，CRF拮抗剂可以逆转对许多压力源的行为反应。这些结果表明，内源性CRF系统在大脑中可能有一个调解行为反应的压力源的作用。从蓝斑核发出的去甲肾上腺素系统长期以来也被假设参与调节与警觉、唤醒和压力相关的行为结构。药理学、生理学和神经解剖学证据支持CRF-去甲肾上腺素相互作用在蓝斑区域中响应于应激物的重要作用，所述应激物可能是模态特异性的，其中CRF神经元激活蓝斑。可以假设另一种去甲肾上腺素-CRF相互作用可能发生在下丘脑室旁核、终纹床核和杏仁核中央核中前脑去甲肾上腺素系统的终末投射中，其中去甲肾上腺素刺激CRF释放，这样的饲料-前向系统在生物体不仅必须动员垂体肾上腺系统而且必须动员中枢神经系统的情况下可能特别重要，以应对环境挑战。然而，在基本的脑激活系统中的这种前馈机制可能特别容易受到功能障碍的影响，因此可能是涉及对应激源（诸如神经性厌食症、焦虑和情感障碍）的异常反应的各种病理生理状况的关键。(C)1999年生物精神病学学会。
Corticotropin-releasing factor (CRF) and related peptides in the central nervous system appears to have activating properties on behavior and to enhance behavioral responses to stressors. CRF and urocortin injected into the brain produces increases in arousal as measured by locomotor activation and increased responsiveness to stressful stimuli. These effects of CRF appear to be independent of the pituitary adrenal axis and can be reversed by specific and selective CRF antagonists alpha-helical CRF9-41 and D-Phe CRF12-41. Perhaps more importantly, CRF antagonists can reverse behavioral responses to many stressors. These results suggest that endogenous CRF systems in the brain may have a role in mediating behavioral responses to stressors. Norepinephrine systems emanating from the nucleus locus coeruleus also long have been hypothesized to be involved in mediating behavioral constructs associated with alertness, arousal, and stress. Pharmacologic, physiologic, and neuroanatomic evidence supports an important role for a CRF-norepinephrine interaction in the region of the locus coeruleus in response to stressors that may be modality-specific where CRF neurons activate the locus coeruleus. One may hypothesize that another norepinephrine-CRF interaction may occur in the terminal projections of the forebrain norepinephrine systems in the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala where norepinephrine stimulates CRF release, Such a feed-forward system may be particularly important in situations where an organism must mobilize not only the pituitary adrenal system but also the central nervous system, in response to environmental challenge. However such a feed-forward mechanism in a fundamental brain-activating system may be particularly vulnerable to dysfunction and thus, may be the key to a variety of patho-physiologic conditions involving abnormal responses to stressors such as anorexia nervosa, anxiety, and affective disorders. (C) 1999 Society of Biological Psychiatry.