Department of Psychology, University of Cambridge, Downing Site, Cambridge, UK.
Biomedical Sciences Group: Woman and Child, KU Leuven, Leuven, Belgium.
Lab Anim (NY). 2022 Nov;51(11):293-300. doi: 10.1038/s41684-022-01054-4. Epub 2022 Oct 20.
Post-traumatic stress disorder (PTSD) is a debilitating mental health condition for which current treatments have long-term efficacy in 50% of patients. There is a clear need for better understanding of the mechanisms underlying PTSD and the development of new treatment approaches. Analog trauma procedures in animals, such as the stress-enhanced fear learning (SEFL) procedure, can be used to produce behavioral and neurobiological changes that have validity in modeling PTSD. However, by necessity, the modeling of PTSD in animals requires them to potentially experience pain and suffering. Consistent with the '3Rs' (reduction, refinement and replacement) of animal research, this study aimed to determine whether the SEFL procedure can be refined to reduce potential animal pain and suffering while retaining the same behavioral and neurobiological changes. Here we showed that PTSD-relevant changes could be produced in both behavior and the brain of rats that were group- rather than single-housed and that received lower-magnitude electric shocks in the 'trauma analog' session. We also varied the number of shock exposures in the trauma analog session, finding SEFL-susceptible and SEFL-resilient populations at all levels of shock exposure, but with greater levels of shock increasing the proportion of rats showing the SEFL-susceptible phenotype. These data demonstrate that the SEFL procedure can be used as an animal analog of PTSD with reduced potential pain and suffering to the animals and that variations in the procedure could be used to generate specific proportions of SEFL-susceptible and SEFL-resilient animals in future studies.
创伤后应激障碍（PTSD）是一种使人衰弱的心理健康状况，目前的治疗方法在 50%的患者中有长期疗效。显然，我们需要更好地了解 PTSD 的发病机制，并开发新的治疗方法。动物的创伤后模拟程序，如应激增强的恐惧学习（SEFL）程序，可以用来产生具有 PTSD 模型有效性的行为和神经生物学变化。然而，为了在动物中模拟 PTSD，它们必须经历潜在的疼痛和痛苦。与动物研究的“3R”（减少、优化和替代）原则一致，本研究旨在确定 SEFL 程序是否可以优化，以减少潜在的动物疼痛和痛苦，同时保留相同的行为和神经生物学变化。在这里，我们表明，在“创伤模拟”会议中，群居而非独居且接受较小幅度电击的大鼠，其行为和大脑中会产生与 PTSD 相关的变化。我们还改变了“创伤模拟”会议中电击暴露的次数，发现所有电击暴露水平均存在 SEFL 易感和 SEFL 抗性群体，但随着电击水平的增加，表现出 SEFL 易感表型的大鼠比例增加。这些数据表明，SEFL 程序可用作 PTSD 的动物模拟，减少了动物的潜在疼痛和痛苦，并且该程序的变化可用于在未来的研究中产生特定比例的 SEFL 易感和 SEFL 抗性动物。
