The role of corticotropin-releasing hormone in the dorsal raphe nucleus in mediating the behavioral consequences of uncontrollable stress
The role of corticotropin-releasing hormone in the dorsal raphe nucleus in mediating the behavioral consequences of uncontrollable stress
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DOI：
10.1523/jneurosci.22-03-01020.2002
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发表时间：
2002-02-01
影响因子：
5.3
通讯作者：
Maier, SF
中科院分区：
文献类型：
--
作者：
Hammack, SE;Richey, KJ;Maier, SF
不可避免的电击（IS）会对逃避行为产生干扰，并增加恐惧条件反射，这与在IS和随后的行为测试时尾侧中隔背核（DRN）神经元中5-羟色胺（5-HT）的活性和释放增加有关。下丘脑外促肾上腺皮质激素释放激素（CRH）与许多应激相关的现象有关，最近研究表明，在IS增加5-羟色胺活性的同一尾侧DRN区域，CRH可增加DRN 5-羟色胺活性。因此，目前的一系列研究检查了CRH在介导IS行为后遗症中的作用。非选择性CRH受体拮抗剂D-Phe CRH（12-41）在drn内显微注射阻断IS诱导的行为改变，但在随后的行为测试之前没有阻断。此外，在没有IS的情况下，CRH在drn内的剂量依赖性模拟了IS的影响，并在24小时后干扰了逃跑行为和增加了恐惧条件反射。这种作用是在尾侧DRN中注射CRH所特有的，而不是在吻侧DRN中注射CRH所产生的。脑室内CRH在24小时后仅在高剂量下产生逃逸缺陷和增强恐惧条件反射，进一步证实了效应的部位特异性。讨论了尾侧DRN在焦虑状态中的潜在作用。
Inescapable shock (IS) produces subsequent interference with escape behavior and increased fear conditioning that has been linked to increased activity and release of serotonin (5-HT) from neurons within the caudal dorsal raphe nucleus (DRN) both at the time of IS and later behavioral testing. Extrahypothalamic corticotropin-releasing hormone (CRH) has been implicated in many stress-related phenomena and has recently been shown to increase DRN 5-HT activity in the same caudal DRN area at which IS increases 5-HT activity. The current set of studies therefore examined the role of CRH in mediating the behavioral sequelae of IS. Intra-DRN microinjection of the nonselective CRH receptor antagonist D-Phe CRH (12-41) blocked the IS-induced behavioral changes when administered before IS but not when administered before later behavioral testing. Furthermore, intra-DRN administration of CRH in the absence of IS dose-dependently mimicked the effects of IS and interfered with escape behavior and increased fear conditioning 24 hr later. This effect was specific to injection of CRH into the caudal DRN and was not produced by microinjection into the rostral DRN. Intracerebroventricular CRH produced escape deficits and potentiated fear conditioning 24 hr later at only much higher doses, further confirming the site specificity of the effects. The potential role of the caudal DRN in states of anxiety is discussed.