Zhang Lei, Hu Xian-Zhang, Li He, Li Xiaoxia, Yu Tianzheng, Dohl Jacob, Ursano Robert J
Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Department of Military and Emergency Medicine, Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Methods Mol Biol. 2019;2011:331-344. doi: 10.1007/978-1-4939-9554-7_19.
Post-traumatic stress disorder (PTSD) is a chronic, debilitating mental disorder afflicting more than 7% of the US population and 12% of military service members. Since the Afghanistan and Iraq wars, thousands of US service members have returned home with PTSD. Despite recent progress, the molecular mechanisms underlying the pathology of PTSD are poorly understood. To promote research on PTSD (especially its molecular mechanisms) and to set a molecular basis for discovering novel medications for this disorder, well-validated animal models are needed. However, to develop PTSD animal models is a challenging process, due to predisposing factors such as physiological, behavioral, emotional, and cognitive changes that emerge after trauma. Currently, there is no well-validated animal model of PTSD, although several stress paradigms mimic the behavioral symptoms and neurological alterations seen in PTSD. In this chapter, we will provide an overview of animal models of PTSD including learned helplessness, footshock, restraint stress, inescapable tail shock, single-prolonged stress, underwater trauma, social isolation, social defeat, early-life stress, and predator-based stress. We emphasize rodent models because they reproduce some of the behavioral and biotical phenotypes seen in PTSD. We will also present data showing that homologous biological measures are increasingly incorporated in studies to assess markers of risk and therapeutic response in these models. Therefore, PTSD animal models may be refined in hopes of capitalizing on the understanding of the molecular mechanisms and delivering tools in order to develop new and more efficacious treatments for PTSD.
创伤后应激障碍（PTSD）是一种慢性、使人衰弱的精神障碍，折磨着超过7%的美国人口和12%的军人。自阿富汗和伊拉克战争以来，数以千计的美国军人带着创伤后应激障碍返回家园。尽管最近取得了进展，但创伤后应激障碍病理背后的分子机制仍知之甚少。为了促进对创伤后应激障碍（尤其是其分子机制）的研究，并为发现针对这种疾病的新型药物奠定分子基础，需要经过充分验证的动物模型。然而，由于创伤后出现的生理、行为、情绪和认知变化等易感因素，开发创伤后应激障碍动物模型是一个具有挑战性的过程。目前，虽然有几种应激范式模拟了创伤后应激障碍中出现的行为症状和神经学改变，但尚无经过充分验证的创伤后应激障碍动物模型。在本章中，我们将概述创伤后应激障碍的动物模型，包括习得性无助、足部电击、束缚应激、不可逃避的尾部电击、单次长时间应激、水下创伤、社会隔离、社会挫败、早期生活应激和基于捕食者的应激。我们着重介绍啮齿动物模型，因为它们再现了创伤后应激障碍中出现的一些行为和生物学表型。我们还将展示数据，表明同源生物学测量方法越来越多地被纳入研究，以评估这些模型中的风险标志物和治疗反应。因此，创伤后应激障碍动物模型可能会得到改进，以期利用对分子机制的理解并提供工具，从而开发出针对创伤后应激障碍的更新、更有效的治疗方法。
