CRF receptor blockade prevents initiation and consolidation of stress effects on affect in the predator stress model of PTSD.
CRF receptor blockade prevents initiation and consolidation of stress effects on affect in the predator stress model of PTSD.
复制标题
DOI：
10.1017/s1461145709990496
复制
发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Risbrough V
中科院分区：
文献类型：
--
作者：
Adamec R;Fougere D;Risbrough V
创伤后应激障碍（PTSD）是一种慢性焦虑症，由强烈的威胁性创伤事件引发。对于PTSD的更有效的药物治疗和预防性治疗存在巨大的需求。在动物中，促肾上腺皮质激素释放因子（CRF）和CRF1受体在应激的行为和神经内分泌反应中起着关键作用。我们测试的假设，CRF1激活所需的启动和巩固的长期影响的创伤焦虑样行为的捕食者暴露（捕食者压力）模型的PTSD。雄性C57BL6小鼠在捕食者应激之前或之后30分钟用选择性CRF1拮抗剂CRA0450（2、20 mg/kg）处理。7 d后，采用声惊吓、高架十字迷宫、光/暗箱和洞板试验测量应激对啮齿动物焦虑的长期影响。捕食者压力增加惊吓幅度和延迟惊吓习惯化，增加时间，减少出口从暗室中的光/暗箱测试，并降低风险评估的风险。CRF1拮抗作用对非应激对照组的这些行为影响有限，高剂量降低了试验组的风险评估。然而，在应激动物中，CRF1拮抗作用阻断了应激源对惊吓的影响的启动和巩固，并使捕食者应激小鼠的风险评估恢复到基线水平。这些研究结果表明，CRF1激活在启动和创伤后巩固捕食者压力对焦虑样行为的影响，特别是对增加的觉醒，通过夸大的惊吓行为来测量。这些数据支持CRF1拮抗剂作为PTSD潜在预防性治疗的进一步研究。
Post traumatic stress disorder (PTSD) is a chronic anxiety disorder initiated by an intensely threatening, traumatic event. There is a great need for more efficacious pharmacotherapy and preventive treatments for PTSD. In animals, corticotropin-releasing factor (CRF) and the CRF1 receptor play a critical role in behavioural and neuroendocrine responses to stress. We tested the hypothesis that CRF1 activation is required for initiation and consolidation of long-term effects of trauma on anxiety-like behaviour in the predator exposure (predator stress) model of PTSD. Male C57BL6 mice were treated with the selective CRF1 antagonist CRA0450 (2, 20 mg/kg) 30 min before or just after predator stress. Long-term effects of stress on rodent anxiety were measured 7 d later using acoustic startle, elevated plus maze (EPM), light/dark box, and hole-board tests. Predator stress increased startle amplitude and delayed startle habituation, increased time in and decreased exits from the dark chamber in the light/dark box test, and decreased risk assessment in the EPM. CRF1 antagonism had limited effects on these behaviours in non-stressed controls, with the high dose decreasing risk assessment in the EPM. However, in stressed animals CRF1 antagonism blocked initiation and consolidation of stressor effects on startle, and returned risk assessment to baseline levels in predator-stressed mice. These findings implicate CRF1 activation in initiation and post-trauma consolidation of predator stress effects on anxiety-like behaviour, specifically on increased arousal as measured by exaggerated startle behaviours. These data support further research of CRF1 antagonists as potential prophylactic treatments for PTSD.