Chiacchierini Giulia, Mancini Giulia Federica, Di Cesare Benedetta, Romanelli Luca, Morena Maria, Campolongo Patrizia
Dept. of Physiology and Pharmacology, Sapienza University of Rome, Rome 00185, Italy; Neuropharmacology Unit, IRCCS Santa Lucia Foundation, Rome 00143, Italy.
Dept. of Physiology and Pharmacology, Sapienza University of Rome, Rome 00185, Italy.
J Neurosci Methods. 2025 Apr;416:110380. doi: 10.1016/j.jneumeth.2025.110380. Epub 2025 Jan 26.
Only a small percentage of trauma-exposed subjects develop PTSD, with females being twice as likely. Most rodent models focus on males and fail to account for inter-individual variability in females.
We tested a behavioral PTSD model in female rats to distinguish between susceptible and resilient individuals. In Experiment 1, female rats underwent footshocks paired with social isolation, a PTSD risk factor. They were re-exposed to the conditioned context to test memory retention, and assessed in the Elevated Plus Maze (EPM) and Social Interaction (SI) tests for anxiety and social behavior.
Footshock-exposed rats showed fear memory retention up to 16 days, indicated by elevated freezing behavior during re-exposure. They also exhibited reduced exploration in the EPM and less SI time compared to controls. In Experiment 2, we classified rats into normal responders, susceptible, and resilient groups based on locomotor activity after trauma, correlating with memory retention and anxiety.
Unlike existing models focused on males and lacking predictive variables before trauma, our method identifies PTSD-like susceptibility and resilience in female rats by using exploratory behavior as a predictor before trauma exposure.
Exploratory activity in a novel environment after trauma and before extinction is a reliable predictor of PTSD-like phenotypes and differentiates between susceptible and resilient female rats.
仅有一小部分经历创伤的个体患上创伤后应激障碍(PTSD),女性患病几率是男性的两倍。大多数啮齿动物模型聚焦于雄性,未考虑雌性个体间的差异。
我们在雌性大鼠中测试了一种行为PTSD模型,以区分易感性个体和恢复力强的个体。在实验1中,雌性大鼠接受与社会隔离配对的足部电击,社会隔离是PTSD的一个风险因素。它们再次暴露于条件化情境中以测试记忆保持情况,并在高架十字迷宫(EPM)和社交互动(SI)测试中评估焦虑和社交行为。
接受足部电击的大鼠在长达16天的时间里表现出恐惧记忆保持,再次暴露期间冻结行为增加表明了这一点。与对照组相比,它们在EPM中的探索行为也减少,社交互动时间也更少。在实验2中,我们根据创伤后的运动活动将大鼠分为正常反应者、易感和恢复力强的组,这与记忆保持和焦虑相关。
与现有聚焦于雄性且缺乏创伤前预测变量的模型不同,我们的方法通过在创伤暴露前将探索行为作为预测指标,识别雌性大鼠中类似PTSD的易感性和恢复力。
创伤后且在消退前在新环境中的探索活动是类似PTSD表型的可靠预测指标,可区分易感和恢复力强的雌性大鼠。