Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Neuropharmacology. 2012 Nov;63(6):1118-26. doi: 10.1016/j.neuropharm.2012.07.034. Epub 2012 Jul 25.
Exposure to psychological trauma is the precipitating factor for PTSD. In addition, a history of chronic or traumatic stress exposure is a predisposing risk factor. We have developed a Chronic plus Acute Prolonged Stress (CAPS) treatment for rats that models some of the characteristics of stressful events that can lead to PTSD in humans. We have previously shown that CAPS enhances acute fear responses and impairs extinction of conditioned fear. Further, CAPS reduced the expression of glucocorticoid receptors in the medial prefrontal cortex. In this study we examined the effects of CAPS exposure on behavioral stress coping style, anxiety-like behaviors, and acute stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Male Sprague-Dawley rats were exposed to CAPS treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/day, 14 days) followed on day 15 by a single 1-h session of sequential acute stressors (social defeat, immobilization, swim). After CAPS or control treatment, different groups were tested for shock probe defensive burying, novelty suppressed feeding, or evoked activation of adrenocorticotropic hormone (ACTH) and corticosterone release by an acute immobilization stress. CAPS resulted in a decrease in active burying behavior and an increase in immobility in the shock probe test. Further, CAPS-treated rats displayed increases in the latency to feed in the novelty suppressed feeding test, despite an increase in food intake in the home cage. CAPS treatment also reduced the HPA response to a subsequent acute immobilization stress. These results further validate CAPS treatment as a rat model of relevance to PTSD, and together with results reported previously, suggest that CAPS impairs fear extinction, shifts coping behavior from an active to a more passive strategy, increases anxiety, and alters HPA reactivity, resembling many aspects of human PTSD.
暴露于心理创伤是 PTSD 的诱发因素。此外，慢性或创伤性应激暴露史是一个易感风险因素。我们已经开发了一种用于大鼠的慢性加急性延长应激（CAPS）治疗方法，该方法模拟了一些可能导致人类 PTSD 的应激事件的特征。我们之前已经表明，CAPS 增强了急性恐惧反应，并损害了条件性恐惧的消退。此外，CAPS 减少了内侧前额叶皮质中糖皮质激素受体的表达。在这项研究中，我们研究了 CAPS 暴露对行为应激应对方式、焦虑样行为以及下丘脑-垂体-肾上腺（HPA）轴的急性应激反应的影响。雄性 Sprague-Dawley 大鼠接受 CAPS 治疗，包括慢性间歇性冷应激（4°C，6 小时/天，14 天），然后在第 15 天接受单次 1 小时的连续急性应激源（社交挫败、固定、游泳）。在 CAPS 或对照治疗后，不同组进行了电击探针防御掩埋、新奇抑制性摄食或急性固定应激诱发的促肾上腺皮质激素（ACTH）和皮质酮释放的测试。CAPS 导致主动掩埋行为减少和电击探针测试中不动性增加。此外，CAPS 处理的大鼠在新奇抑制性摄食测试中显示出进食潜伏期增加，尽管在笼内进食增加。CAPS 处理还降低了随后急性固定应激的 HPA 反应。这些结果进一步验证了 CAPS 治疗作为 PTSD 相关大鼠模型的有效性，并且与之前报告的结果一起表明，CAPS 损害了恐惧消退，将应对行为从主动策略转变为更被动的策略，增加了焦虑，并改变了 HPA 反应，类似于人类 PTSD 的许多方面。
