Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats
Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats
复制标题
DOI：
10.1007/s00213-008-1179-7
复制
发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Lucki, Irwin
中科院分区：
文献类型：
--
作者：
Howard, Owen;Carr, Gregory V.;Lucki, Irwin
基本原理中央行政促肾上腺皮质激素释放因子（CRF）elarned一个特定的模式的行为反应类似于一个压力样的状态，是anxiogenic在啮齿动物模型anxious.Objectives的管理引起的CRF的具体行为进行了测量。CRF受体亚型的作用，并在介导这些responses.Materials and Methods的肾上腺素能和去甲肾上腺素能系统的CRF和urocortin II和预处理后拮抗剂脑室内给药的大鼠埋，梳理，和摇头进行了量化。前脑去甲肾上腺素在CRF（0.3 μ g）的行为反应的作用进行了检查后预处理的神经毒素DSP-4和5-羟色胺耗尽后使用全身给药的对氯苯丙氨酸（p-CPA）。结果CRF在0.3和3.0 μ g引起的埋葬，梳理，和摇头，但urocortin II是无效的。安他拉明或普萘洛尔预处理显着减弱了CRF诱发的行为。前脑去甲肾上腺素通路的破坏阻断自发埋藏行为引起的CRF和条件埋藏指向一个通电的冲击探头。与此相反，5-HT的耗竭选择性衰减CRF诱发grooming.Conclusions CRF，掩埋，梳理，和摇头产生的明显的行为反应似乎是通过CRF 1受体介导的。自发埋藏行为引起的CRF或条件埋藏直接对一个冲击探头被破坏的背侧去甲肾上腺素能束的病变，并可能代表焦虑样行为所造成的CRF激活蓝斑。相反，CRF诱发的梳理增加依赖于5-羟色胺。
Rationale Central administration of corticotropin-releasing factor (CRF) elicits a specific pattern of behavioral responses resembling a stress-like state and is anxiogenic in rodent models of anxiety.Objectives Specific behaviors evoked by the administration of CRF were measured. The roles of CRF receptor subtypes and that of serotonergic and noradrenergic systems in mediating these responses were studied.Materials and methods Burying, grooming, and head shakes were quantified in rats following intracerebroventricular administration of CRF and urocortin II and after pretreatment with antagonists. The role of forebrain norepinephrine in the behavioral responses to CRF (0.3 mu g) was examined following pretreatment with the neurotoxin DSP-4 and that of serotonin after depletion using systemic administration of para-chlorophenylalanine (p-CPA).Results CRF at 0.3 and 3.0 mu g caused robust increases in burying, grooming, and head shakes, but urocortin II was ineffective. Pretreatment with either antalarmin or propranolol significantly attenuated the CRF-evoked behaviors. Destruction of forebrain norepinephrine pathways blocked spontaneous burying behavior elicited by CRF and conditioned burying directed towards an electrified shock probe. In contrast, depletion of 5-HT selectively attenuated CRF-evoked grooming.Conclusions Overt behavioral responses produced by CRF, burying, grooming, and head shakes appeared to be mediated through the CRF1 receptor. Spontaneous burying behavior evoked by CRF or conditioned burying directed towards a shock probe was disrupted by lesion of the dorsal noradrenergic bundle and may represent anxiety-like behavior caused by CRF activation of the locus ceruleus. In contrast, CRF-evoked increases in grooming were dependent on serotonin.