The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress
The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress
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DOI：
10.1210/en.140.1.79
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发表时间：
1999-01-01
期刊：
影响因子：
4.8
通讯作者：
Gold, PW
中科院分区：
文献类型：
--
作者：
Deak, T;Nguyen, KT;Gold, PW
非肽类CRH拮抗剂antalarmin已被证明可以阻断对CRH的行为和内分泌反应。然而，它的潜在活动在钝化行为和内分泌后遗症的压力暴露尚未得到评估。由于α-螺旋CRH对中枢CRH的拮抗作用减弱了条件性恐惧反应，我们试图在这方面测试antalarmin。此外，目前尚不清楚这是否是在调节或测试期间受体阻断的结果。因此，我们探讨了CRH是否介导了条件性恐惧的诱导或表达（在先前与2次足电击相关的背景下冻结; 1.0 mA，每次5秒）。此外，由于大鼠先前暴露于不可避免的休克（IS; 100次休克，1.6 mA，每次5秒），表现出增强的恐惧条件反射，我们研究了这种作用是否会被antalarmin阻断。Antalarmin（20毫克/公斤。2毫升IP）的诱导和表达条件性恐惧受损。此外，antalarmin阻断了先前暴露于IS所产生的恐惧条件反射的增强。尽管在antalarmin处理的大鼠中观察到显著的行为效应，但antalarmin对IS诱导的ACTH或皮质酮升高没有影响。然而，antalarmin确实阻断了暴露于2次足电击产生的ACTH反应。
The nonpeptide CRH antagonist antalarmin has been shown to block both behavioral and endocrine responses to CRH. However, it's potential activity in blunting behavioral and endocrine sequelae of stressor exposure has not been assessed. Because antagonism of central CRH by alpha-helical CRH attenuates conditioned fear responses, we sought to test antalarmin in this regard. In addition, it remains unclear as to whether this is a result of receptor blockade during conditioning or during testing. Thus, we explored whether CRH mediates the induction or expression of conditioned fear (freezing in a context previously associated with 2 footshocks; 1.0 mA, 5 sec each). Furthermore, because rats previously exposed to inescapable shock (IS; 100 shocks, 1.6 mA, 5 sec each), demonstrate enhanced fear conditioning, we investigated whether this effect would be blocked by antalarmin. Antalarmin (20 mg/kg.2 mi ip) impaired both the induction and expression of conditioned fear. In addition, antalarmin blocked the enhancement of fear conditioning produced by prior exposure to IS. Despite the marked behavioral effects observed in antalarmin-treated rats, antalarmin had no effect on IS-induced rises in ACTH or corticosterone. However, antalarmin did block the ACTH response produced by exposure to 2 footshocks.