CRF1 and CRF2 receptors are required for potentiated startle to contextual but not discrete cues.
CRF1 and CRF2 receptors are required for potentiated startle to contextual but not discrete cues.
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DOI：
10.1038/npp.2008.205
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发表时间：
2009-05
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影响因子：
--
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促肾上腺皮质激素释放因子（CRF）肽及其受体在应激的行为和内分泌反应中具有重要作用。CRF信号的失调与创伤后应激障碍有关，创伤后应激障碍与对威胁的惊吓反应增加有关。因此，了解CRF调节惊吓的机制可能会发现参与这种疾病的途径。在这里，我们测试了CRF1和CRF2受体都有助于恐惧诱导的惊吓增加的假设。在足电击（电击致敏）后或在存在先前与足电击相关的线索（即恐惧增强惊吓，FPS）的情况下，立即测量野生型（WT）和CRF1或CRF2受体基因无效突变（敲除，KO）小鼠的惊吓反应。WT小鼠在电击足后立即表现出强烈的惊吓增加，这取决于上下文线索。这种效应在CRF1 KO小鼠中完全不存在，在CRF2 KO小鼠中显著减弱。相反，CRF1和CRF2基因敲除小鼠表现出正常的增强惊吓离散条件的线索。在CRF2 KO小鼠中，通过CRF1受体拮抗剂治疗阻断两种受体对FPS也没有影响。这些结果支持CRF1和CRF2受体激活对增强惊吓作用的加性模型。这些数据还表明，CRF受体亚型有助于上下文的恐惧，但不需要离散线索恐惧惊吓反应的影响。因此，我们认为，CRF1或CRF2可能有助于增加惊恐与CRF系统异常的焦虑症。
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.
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影响因子：
5.3
作者：
Henry, Brook;Vale, Wylie;Markou, Athina
通讯作者：
Markou, Athina
影响因子：
3.3
作者：
Hubbard, D. T.;Nakashima, B. R.;Takahashi, L. K.
通讯作者：
Takahashi, L. K.
影响因子：
3
作者：
Hauger, Richard L.;Risbrough, Victoria;Dautzenberg, Frank M.
通讯作者：
Dautzenberg, Frank M.
影响因子：
3.7
作者：
GRAHAM, FK
通讯作者：
GRAHAM, FK
DOI：
10.1037//0097-7403.4.2.95
发表时间：
1978-01-01
期刊：
JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIORAL PROCESSES
影响因子：
--
作者：
DAVIS, M;ASTRACHAN, DI
通讯作者：
ASTRACHAN, DI