Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain
Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain
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DOI：
10.1038/npp.2014.117
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发表时间：
2014-10-01
影响因子：
7.6
通讯作者：
Greenwood-Van Meerveld, Beverley
中科院分区：
文献类型：
--
作者：
Lee Tran;Schulkin, Jay;Greenwood-Van Meerveld, Beverley
终纹床核 (BNST) 中促肾上腺皮质激素释放因子 (CRF) 介导的机制在应激引起的焦虑和痛觉过敏中发挥着关键作用。尽管已知 CRF 可以激活两种受体亚型：CRF1 和 CRF2，但描述每种亚型在调节焦虑和伤害感受中具体作用的尝试却不一致。在这里，我们检验了这样的假设：前外侧 BNST (BNSTAL) 中的 CRF1 和 CRF2 受体激活有助于调节共病焦虑和痛觉过敏的不同机制。将特定拮抗剂 CP376395 和 Astressin(2)B 微量输注至 BNSTAL 中，分别用于研究 CRF1 和 CRF2 受体功能。我们发现 BNSTAL 中的 CRF1 和 CRF2 受体对高架十字迷宫中的探索行为、躯体机械阈值以及对压力的自主和内分泌反应具有相反的影响。然而，BNSTAL 中的 CRF1 或 CRF2 受体拮抗作用揭示了在促进听觉惊吓和内脏运动反射方面的互补作用。我们的结果表明，BNSTAL 中 CRF1 和 CRF2 受体激活的净效应是通路依赖性的，并为可能支持应激诱发病理的 CRF 受体相关电路提供了重要的见解。
Corticotropin-releasing factor (CRF)-mediated mechanisms in the bed nucleus of the stria terminalis (BNST) have a pivotal role in stress-induced anxiety and hyperalgesia. Although CRF is known to activate two receptor subtypes, CRF1 and CRF2, attempts to delineate the specific role of each subtype in modulating anxiety and nociception have been inconsistent. Here we test the hypothesis that CRF1 and CRF2 receptor activation in the anteriolateral BNST (BNSTAL) facilitates divergent mechanisms modulating comorbid anxiety and hyperalgesia. Microinfusions of the specific antagonists CP376395 and Astressin(2)B into the BNSTAL were used to investigate CRF1 and CRF2 receptor functions, respectively. We found that CRF1 and CRF2 receptors in the BNSTAL had opposing effects on exploratory behavior in the elevated plus-maze, somatic mechanical threshold, and the autonomic and endocrine response to stress. However, CRF1 or CRF2 receptor antagonism in the BNSTAL revealed complementary roles in facilitating the acoustic startle and visceromotor reflexes. Our results suggest that the net effect of CRF1 and CRF2 receptor activation in the BNSTAL is pathway-dependent and provides important insight into the CRF receptor-associated circuitry that likely underpins stress-induced pathologies.