Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
Neurobiology of Behavior Laboratory, Santa Lucia Foundation, 00143, Rome, Italy.
Transl Psychiatry. 2020 Jul 21;10(1):243. doi: 10.1038/s41398-020-00929-9.
Post-traumatic stress disorder (PTSD) is a psychiatric disorder whose pathogenesis relies on a maladaptive expression of the memory for a life-threatening experience, characterized by over-consolidation, generalization, and impaired extinction, which are responsible of dramatic changes in arousal, mood, anxiety, and social behavior. Even if subjects experiencing a traumatic event during lifetime all show an acute response to the trauma, only a subset of them (susceptible) ultimately develops PTSD, meanwhile the others (resilient) fully recover after the first acute response. However, the dynamic relationships between the interacting brain circuits that might potentially link trauma-related experiences to the emergence of susceptible and resilient PTSD phenotypes in individuals is not well understood. Toward the first step to reach this goal, we have implemented our experimental PTSD model previously developed, making it suitable to differentiate between susceptible (high responders, HR) and resilient (low responders, LR) rats in terms of over-consolidation, impaired extinction, and social impairment long after trauma. Rats were exposed to five footshocks paired with social isolation. One week after trauma but before extinction, animals were tested in the Open Field and Social Interaction tasks for the identification of a predictive variable to identify susceptible and resilient animals before the possible appearance of a PTSD-like phenotype. Our findings show that exploratory activity after trauma in a novel environment is a very robust variable to predict susceptibility towards a PTSD-like phenotype. This experimental model is thus able to screen and differentiate, before extinction learning and potential therapeutic intervention, susceptible and resilient PTSD-like rats.
创伤后应激障碍（PTSD）是一种精神障碍，其发病机制依赖于对危及生命的经历的记忆的适应不良表达，其特征是过度巩固、泛化和消退受损，这导致了觉醒、情绪、焦虑和社会行为的剧烈变化。即使一生中经历创伤事件的受试者都对创伤有急性反应，但只有其中一部分（易感）最终会发展为 PTSD，而其他人（有弹性）在首次急性反应后完全恢复。然而，相互作用的大脑回路之间的动态关系，这些回路可能将与创伤相关的经历与个体易感和有弹性 PTSD 表型的出现联系起来，目前还不是很清楚。为了实现这一目标的第一步，我们已经实施了我们之前开发的 PTSD 实验模型，使其能够根据过度巩固、消退受损和社交障碍，在创伤后很长一段时间内区分易感（高反应者，HR）和有弹性（低反应者，LR）大鼠。大鼠接受五次与社交隔离配对的足底电击。创伤后一周但在消退前，动物在开阔场和社交互动任务中进行测试，以确定一个预测变量，以便在可能出现 PTSD 样表型之前识别易感和有弹性的动物。我们的研究结果表明，创伤后在新环境中的探索性活动是预测 PTSD 样表型易感性的一个非常可靠的变量。因此，这种实验模型能够在消退学习和潜在的治疗干预之前筛选和区分易感和有弹性的 PTSD 样大鼠。
