THE ROLE OF LIMBIC AND HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR IN BEHAVIORAL-RESPONSES TO STRESS
THE ROLE OF LIMBIC AND HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR IN BEHAVIORAL-RESPONSES TO STRESS
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DOI：
10.1111/j.1749-6632.1993.tb49929.x
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发表时间：
1993-01-01
期刊：
影响因子：
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通讯作者：
KOOB, GF
中科院分区：
文献类型：
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作者：
MENZAGHI, F;HEINRICHS, SC;KOOB, GF
中枢神经系统中的CRF似乎对行为具有激活特性，并协调对压力的行为反应。CRF的这些行为效应似乎不依赖于垂体-肾上腺轴，并且可以被一种CRF拮抗剂（α -螺旋CRF9-41）逆转。CRF拮抗剂不仅逆转与压力相关的行为减少，而且还逆转与压力相关的行为增加，从而表明CRF的作用依赖于压力，而不是固有的给定行为反应。此外，α -螺旋CRF9-41的显微注射和单独脑室中CRF神经元的免疫靶向表明，含有CRF的解剖部位与应激行为反应的性质之间存在联系，这种联系可以通过抑制内源性CRF活性来改变。因此，与其他下丘脑释放因子在整合激素和神经机制方面的双重作用一致，CRF可以作为垂体前叶激素的分泌剂和垂体外肽神经递质，在几个身体水平上协调应对应激反应（图6）。此外，这种基本体内平衡系统的功能障碍可能是包括精神障碍在内的各种病理生理状况的关键。
CRF in the central nervous system appears to have activating properties on behavior and to coordinate behavioral responses to stress. These behavioral effects of CRF appear to be independent of the pituitary-adrenal axis and can be reversed by a CRF antagonist, alpha-helical CRF9-41. The CRF antagonist reverses not only decreases in behavior associated with stress, but also increases in behavior associated with stress, thus suggesting that the role of CRF is stress dependent and not intrinsic to a given behavioral response. Further, microinjection of alpha-helical CRF9-41 and immunotargeting of CRF neurons in separate brain compartments reveal a link between the anatomical sites that contain CRF and the nature of the behavioral response to stress that can be modified by suppression of endogenous CRF activity therein. Hence, consistent with the dual role of other hypothalamic-releasing factors in integrating hormonal and neural mechanisms by acting both as secretagogues for anterior pituitary hormones and as extrapituitary peptide neurotransmitters, CRF may coordinate coping responses to stress at several bodily levels (Fig. 6). Moreover, dysfunction in such a fundamental homeostatic system may be the key to a variety of pathophysiological conditions including mental disorders.