Memorial University, St. John's, Newfoundland, Canada.
Physiol Behav. 2012 Feb 1;105(3):628-38. doi: 10.1016/j.physbeh.2011.09.016. Epub 2011 Sep 24.
This study had two purposes. First: to compare predator and water submersion stress cFos activation in medial prefrontal cortices (mPFC) and the medial amygdala (MeA). Second: to identify markers of vulnerability to stressors within these areas. Rats were either predator or submersion stressed and tested 1.75 h later for anxiety. Immediately thereafter, rats were sacrificed and cFos expression was examined. Predator and submersion stress equally increased anxiety-like behavior in the elevated plus maze (EPM) and hole board. To examine vulnerability, rats which were less anxious (LA) and more (highly) anxious (MA) in the EPM were selected from among handled control and stressed animals. LA stressed rats were considered stress non-responsive while MA stressed rats were considered stress responsive. Predator stress, but not submersion stress, activated MeA cFos. CFos expression of mPFC cells was elevated in LA rats and reduced in MA rats in predator stressed animals only, correlating negatively with anxiety. These findings are consistent with data implicating greater mPFC excitability in protection against the effects on affect of traumatic stress. The findings also suggest that this conclusion is stressor specific, applying to predator stress but not submersion stress. Both stressors have been suggested to model hyperarousal and comorbid anxiety aspects of PTSD in humans. Hence the use of these paradigms to identify brain bases of vulnerability and resilience to traumatic stress in PTSD has translation potential. On the other hand, our evidence of stressor specificity of vulnerability/resilience markers raises a caution. The data suggest that preclinical markers of vulnerability/resilience in a given stress paradigm are at best suggestive, and translational value must ultimately be confirmed in humans.
这项研究有两个目的。第一：比较捕食者和水淹没应激 cFos 在中前额皮质（mPFC）和内侧杏仁核（MeA）中的激活。第二：确定这些区域内易受压力源影响的标志物。大鼠要么受到捕食者压力，要么受到淹没压力，并在 1.75 小时后进行焦虑测试。随后，立即处死大鼠并检查 cFos 表达。捕食者和淹没应激同样增加了高架十字迷宫（EPM）和洞板中的焦虑样行为。为了检查易感性，从处理过的对照动物和应激动物中选择在 EPM 中焦虑程度较低（LA）和较高（MA）的大鼠。LA 应激大鼠被认为对压力无反应，而 MA 应激大鼠被认为对压力有反应。捕食者应激，但不是淹没应激，激活了 MeA 的 cFos。仅在捕食者应激动物中，LA 大鼠的 mPFC 细胞 cFos 表达升高，而 MA 大鼠的 cFos 表达降低，与焦虑呈负相关。这些发现与暗示更大的 mPFC 兴奋性可保护创伤应激对情感的影响的数据一致。这些发现还表明，这一结论是应激特异性的，适用于捕食者应激，但不适用于淹没应激。这两种应激都被认为可以模拟 PTSD 中人类的过度唤醒和共病焦虑方面。因此，这些范式的使用可以识别 PTSD 中创伤应激易感性和弹性的大脑基础具有转化潜力。另一方面，我们关于易感性/弹性标志物应激特异性的证据引起了注意。这些数据表明，在特定应激范式中易感性/弹性的临床前标志物最多只是提示性的，并且转化价值最终必须在人类中得到证实。
