创伤后应激障碍的啮齿类动物模型:行为评估。
Rodent models of post-traumatic stress disorder: behavioral assessment.
机构信息
Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, 16802, USA.
Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
出版信息
Transl Psychiatry. 2020 May 6;10(1):132. doi: 10.1038/s41398-020-0806-x.
Although the etiology and expression of psychiatric disorders are complex, mammals show biologically preserved behavioral and neurobiological responses to valent stimuli which underlie the use of rodent models of post-traumatic stress disorder (PTSD). PTSD is a complex phenotype that is difficult to model in rodents because it is diagnosed by patient interview and influenced by both environmental and genetic factors. However, given that PTSD results from traumatic experiences, rodent models can simulate stress induction and disorder development. By manipulating stress type, intensity, duration, and frequency, preclinical models reflect core PTSD phenotypes, measured through various behavioral assays. Paradigms precipitate the disorder by applying physical, social, and psychological stressors individually or in combination. This review discusses the methods used to trigger and evaluate PTSD-like phenotypes. It highlights studies employing each stress model and evaluates their translational efficacies against DSM-5, validity criteria, and criteria proposed by Yehuda and Antelman's commentary in 1993. This is intended to aid in paradigm selection by informing readers about rodent models, their benefits to the clinical community, challenges associated with the translational models, and opportunities for future work. To inform PTSD model validity and relevance to human psychopathology, we propose that models incorporate behavioral test batteries, individual differences, sex differences, strain and stock differences, early life stress effects, biomarkers, stringent success criteria for drug development, Research Domain Criteria, technological advances, and cross-species comparisons. We conclude that, despite the challenges, animal studies will be pivotal to advances in understanding PTSD and the neurobiology of stress.
尽管精神疾病的病因和表现复杂,但哺乳动物对有价值的刺激表现出具有生物学保护意义的行为和神经生物学反应,这为创伤后应激障碍(PTSD)的啮齿动物模型的应用提供了基础。PTSD 是一种复杂的表型,很难在啮齿动物中建模,因为它是通过患者访谈诊断的,并受到环境和遗传因素的影响。然而,鉴于 PTSD 是由创伤经历引起的,啮齿动物模型可以模拟应激诱导和疾病发展。通过操纵应激类型、强度、持续时间和频率,临床前模型可以通过各种行为测定来反映 PTSD 的核心表型。通过单独或组合应用生理、社会和心理应激源,范式可以引发疾病。本综述讨论了触发和评估 PTSD 样表型的方法。它强调了使用每种应激模型的研究,并根据 DSM-5、有效性标准以及 Yehuda 和 Antelman 1993 年评论提出的标准,评估了它们对转化的效果。这旨在通过向读者介绍啮齿动物模型、它们对临床社区的益处、转化模型相关的挑战以及未来工作的机会,帮助读者选择范式。为了使 PTSD 模型的有效性和与人类精神病理学的相关性得到信息,我们建议模型纳入行为测试组合、个体差异、性别差异、品系和种群差异、早期生活应激效应、生物标志物、药物开发的严格成功标准、研究领域标准、技术进步和跨物种比较。我们得出结论,尽管存在挑战,但动物研究对于理解 PTSD 和应激的神经生物学将是至关重要的。