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CRF1 and CRF2 Receptors are Required for Potentiated Startle to Contextual but not Discrete Cues

机译：需要CRF1和CRF2受体才能使惊吓语境更准确但不需要离散提示

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Corticotropin-releasing factor (CRF) peptides and their receptors have crucial roles in behavioral and endocrine responses to stress. Dysregulation of CRF signaling has been linked to post-traumatic stress disorder, which is associated with increased startle reactivity in response to threat. Thus, understanding the mechanisms underlying CRF regulation of startle may identify pathways involved in this disorder. Here, we tested the hypothesis that both CRF1 and CRF2 receptors contribute to fear-induced increases in startle. Startle responses of wild type (WT) and mice with null mutations (knockout, KO) for CRF1 or CRF2 receptor genes were measured immediately after footshock (shock sensitization) or in the presence of cues previously associated with footshock (ie fear-potentiated startle, FPS). WT mice exhibited robust increases in startle immediately after footshock, which was dependent upon contextual cues. This effect was completely absent in CRF1 KO mice, and significantly attenuated in CRF2 KO mice. In contrast, CRF1 and CRF2 KO mice exhibited normal potentiation of startle by discrete conditioned cues. Blockade of both receptors via CRF1 receptor antagonist treatment in CRF2 KO mice also had no effect on FPS. These results support an additive model of CRF1 and CRF2 receptor activation effects on potentiated startle. These data also indicate that both CRF receptor subtypes contribute to contextual fear but are not required for discrete cued fear effects on startle reactivity. Thus, we suggest that either CRF1 or CRF2 could contribute to the increased startle observed in anxiety disorders with CRF system abnormalities.
机译：促肾上腺皮质激素释放因子（CRF）肽及其受体在行为和内分泌对压力的反应中起关键作用。 CRF信号转导异常与创伤后应激障碍有关，后者与对威胁的反应引起的惊吓反应性增加有关。因此，了解惊吓的CRF调节的基本机制可能会确定该疾病涉及的途径。在这里，我们测试了CRF1和CRF2受体都有助于恐惧引起的惊吓增加的假说。在发生触电后（触电致敏）或在先前与触电相关的提示（即恐惧增强的触电， FPS）。 WT小鼠在休克后立即表现出惊人的惊吓性增强，这取决于上下文提示。此效应在CRF1 KO小鼠中完全不存在，而在CRF2 KO小鼠中显着减弱。相反，CRF1和CRF2 KO小鼠通过离散条件提示显示出正常的惊吓增强效果。在CRF2 KO小鼠中通过CRF1受体拮抗剂治疗对两种受体的阻断也对FPS没有影响。这些结果支持了CRF1和CRF2受体对增强惊吓的激活作用的累加模型。这些数据还表明，这两种CRF受体亚型均会引起情境恐惧，但对于惊吓反应性的离散暗示恐惧影响并非必需。因此，我们建议在具有CRF系统异常的焦虑症中观察到CRF1或CRF2均可导致惊吓增加。

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