Activation of basolateral amygdala corticotropin-releasing factor 1 receptors modulates the consolidation of contextual fear
Activation of basolateral amygdala corticotropin-releasing factor 1 receptors modulates the consolidation of contextual fear
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DOI：
10.1016/j.neuroscience.2007.10.001
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发表时间：
2007-12-19
期刊：
影响因子：
3.3
通讯作者：
Takahashi, L. K.
中科院分区：
文献类型：
--
作者：
Hubbard, D. T.;Nakashima, B. R.;Takahashi, L. K.
基底外侧杏仁核复合体(BLA)和中央杏仁核(CEA)参与恐惧和焦虑。此外，与CEA相比，BLA含有高密度的促肾上腺皮质激素释放因子1(CRF1)受体。然而，BLA CRF1受体在情景恐惧条件反射中的作用还知之甚少。在本研究中，我们首先在大鼠身上证明，口服选择性CRF1受体拮抗剂DMP696对情景恐惧的获得没有显著影响，但随后在情景冻结中产生了损害，表明CRF1受体在恐惧记忆巩固过程中发挥了作用。此外，在恐惧后条件反射期间，口服DMP696显著减少杏仁外侧核和基底外侧核中环AMP反应元件结合蛋白(PCREB)的磷酸化，但不减少CEA中的磷酸化。然后，我们证明了双侧BLA微量注射DMP696对条件性恐惧的获得没有显著影响，但在随后的非药物条件性恐惧测试中减少了情境冻结。重要的是，在暴露于情景恐惧条件反射后的5分钟或3小时，而不是9小时，双侧脑内微量注射DMP696也能有效地减少条件性恐惧测试中的情景冻结。最后，在CEA中微量注射DMP696或在BLA中注入特定的促肾上腺皮质激素释放因子2受体拮抗剂，在无药物的条件性恐惧测试中，无论是对情境恐惧条件反射还是情境冻结表现都没有重大影响。总之，结果暗示BLA CRF1受体在激活恐惧记忆巩固过程中发挥作用，这可能涉及BLA pCREB诱导的突触可塑性。(C)2007年IBRO。爱思唯尔有限公司出版。保留所有权利。
The basolateral amygdala complex (BLA) and central amygdala nucleus (CeA) are involved in fear and anxiety. In addition, the BLA contains a high density of corticotropin-releasing factor 1 (CRF1) receptors in comparison to the CeA. However, the role of BLA CRF1 receptors in contextual fear conditioning is poorly understood. In the present study, we first demonstrated in rats that oral administration of DMP696, the selective CRF1 receptor antagonist, had no significant effects on the acquisition of contextual fear but produced a subsequent impairment in contextual freezing suggesting a role of CRF1 receptors in the fear memory consolidation process. In addition, oral administration of DMP696 significantly reduced phosphorylation of cyclic AMP response element-binding protein (pCREB) in the lateral and basolateral amygdala nuclei, but not in the CeA, during the post-fear conditioning period. We then demonstrated that bilateral microinjections of DMP696 into the BLA produced no significant effects on the acquisition of conditioned fear but reduced contextual freezing in a subsequent drug-free conditioned fear test. Importantly, bilateral microinjections of DMP696 into the BLA at 5 min or 3 h, but not 9 h, after exposure to contextual fear conditioning was also effective in reducing contextual freezing in the conditioned fear test. Finally, microinfusions of either DMP696 into the CeA or a specific corticotropin-releasing factor 2 receptor antagonist in the BLA were shown to have no major effects on disrupting either contextual fear conditioning or performance of contextual freezing in the drug-free conditioned fear test. Collectively, results implicate a role of BLA CRF1 receptors in activating the fear memory consolidation process, which may involve BLA pCREB-induced synaptic plasticity. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.