ANTISTRESS ACTION OF A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST ON BEHAVIORAL REACTIVITY TO STRESSORS OF VARYING TYPE AND INTENSITY
ANTISTRESS ACTION OF A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST ON BEHAVIORAL REACTIVITY TO STRESSORS OF VARYING TYPE AND INTENSITY
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DOI：
10.1038/sj.npp.1380104
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发表时间：
1994-11-01
影响因子：
7.6
通讯作者：
KOOB, GF
中科院分区：
文献类型：
--
作者：
HEINRICHS, SC;MENZAGHI, F;KOOB, GF
中央管理的促肾上腺皮质激素释放因子（CRF）拮抗剂是有据可查的，以减弱各种行为反应的几个不同的应激源，但是，目前尚不清楚是否激活CRF神经元是依赖于实验应激的类型或强度，或更确切地说，在研究中的特定行为反应的压力。为了测试CRF拮抗剂α-螺旋CRF（9-41）（脑室内1、5或25 μ g）的应激保护作用的一般性，本实验通过测量暴露于社交、游泳或束缚应激源后在高架十字迷宫上探索的抑制，采用了致焦虑样行为的敏感指数。在社交、游泳或束缚应激前给予1 μ g而非5 μ g或25 μ g剂量的CRF拮抗剂可逆转应激诱导的探索行为抑制。利血平和类固醇麻醉剂阿法沙龙也减弱了束缚应激的焦虑样作用，并提高了非应激对照组的基线探索行为。虽然应激源产生的促肾上腺皮质激素（ACTH）的分级分泌与排名限制>游泳>社会，社会，游泳和限制应激的行为反应的相对幅度是可比的。CRF拮抗剂逆转应激效应的相对功效也相当。这些结果表明，激活的脑CRF系统的拮抗作用减弱的行为反应的压力，无论类型或强度的应激源，测定促肾上腺皮质激素分泌。
Central administration of a Corticotropin-Releasing Factor (CRF) antagonist is well documented to attenuate a variety of behavioral responses to several distinct stressors; however, it is not yet clear whether the activation of CRF neurons is dependent on the type or intensity of the experimental stressor, or rather on the particular behavioral response to stress under study. To test the generality of the stress-protective effect of the CRF antagonist, alpha-helical CRF(9-41), (1, 5 or 25 mu g intracerebroventricularly), the present experiments employed a sensitive index of anxiogenic-like behavior by measuring suppression in exploration on the elevated plus-maze following exposure to social, swim, or restraint stressors. A 1 but not 5 or 25 mu g dose of the CRF antagonist administered just prior to social, swim, or restraint stress reversed the stress-induced inhibition of exploratory behavior. Chlordiazepoxide and the steroid anesthetic, alphaxalone, also attenuated the anxiogenic-like effect of restraint stress and elevated the baseline exploratory behavior of nonstressed control groups. Although the stressors produced a graded secretion of adrenocorticotropin (ACTH) with the ranking restraint > swim > social, the relative amplitude of behavioral reactivity to social, swim, and restraint stress was comparable. The relative efficacy of the CRF antagonist to reverse the stressor effects was also comparable. These results suggest that antagonism of activated brain CRF systems attenuates the behavioral response to stress regardless of the type or intensify of the stressor as measured by ACTH secretion.