Albrechet-Souza Lucas, Gilpin Nicholas W
Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Behav Pharmacol. 2019 Apr;30(2 and 3-Spec Issue):105-114. doi: 10.1097/FBP.0000000000000460.
Individuals with post-traumatic stress disorder avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal axis response at the time of trauma. Our laboratory uses predator odor (i.e. bobcat urine) stress to divide adult Wistar rats into groups that exhibit high (avoiders) or low (nonavoiders) avoidance of a predator odor-paired context, modeling the fact that not all humans exposed to traumatic events develop psychiatric conditions. Male avoiders exhibit lower body weight gain after stress, as well as extinction-resistant avoidance that persists after a second stress exposure. These animals also show attenuated hypothalamic-pituitary-adrenal axis response to predator odor that predicts subsequent avoidance of the odor-paired context. Avoiders exhibit unique brain activation profiles relative to nonavoiders and controls (as measured by Fos immunoreactivity), and higher corticotropin-releasing factor levels in multiple brain regions. Furthermore, avoider rats exhibit escalated and compulsive-like alcohol self-administration after traumatic stress. Here, we review the predator odor avoidance model of post-traumatic stress disorder and its utility for tracking behavior and measuring biological outcomes predicted by avoidance. The major strengths of this model are (i) etiological validity with exposure to a single intense stressor, (ii) established approach distinguishing individual differences in stress reactivity, and (iii) robust behavioral and biological phenotypes during and after trauma.
患有创伤后应激障碍的个体避免与创伤相关的刺激，并在创伤发生时表现出下丘脑-垂体-肾上腺轴反应迟钝。我们实验室使用捕食者气味（即山猫尿液）应激，将成年Wistar大鼠分为对捕食者气味配对环境表现出高回避（回避者）或低回避（非回避者）的组，以此模拟并非所有经历创伤事件的人类都会患上精神疾病这一事实。雄性回避者在应激后体重增加较低，并且在第二次应激暴露后仍存在抗消退回避行为。这些动物对捕食者气味的下丘脑-垂体-肾上腺轴反应也减弱，这预示着随后对气味配对环境的回避。与非回避者和对照组相比，回避者表现出独特的大脑激活模式（通过Fos免疫反应性测量），并且在多个脑区中促肾上腺皮质激素释放因子水平更高。此外，回避型大鼠在创伤应激后表现出升级的、强迫样的酒精自我给药行为。在此，我们综述创伤后应激障碍的捕食者气味回避模型及其在追踪行为和测量由回避预测的生物学结果方面的效用。该模型的主要优点包括：（i）暴露于单一强烈应激源时的病因学有效性；（ii）区分应激反应个体差异的既定方法；（iii）创伤期间及之后强大的行为和生物学表型。
