Mancini Giulia Federica, Blasi Eleonora, Marchetta Enrico, Morena Maria, Borgi Marta, Campolongo Patrizia
Dept. of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, Rome 00185, Italy.
Dept. of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, Rome 00185, Italy; Neuropharmacology Unit, IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano 64, Rome 00143, Italy.
Neurosci Biobehav Rev. 2025 Aug;175:106221. doi: 10.1016/j.neubiorev.2025.106221. Epub 2025 May 21.
Pavlovian fear conditioning is a widely used behavioural task for studying fear memory in rodents. During conditioning, rodents learn to associate a conditioned stimulus (e.g., context or tone; contextual or auditory fear conditioning, CFC or AFC, respectively) with an aversive one (e.g., footshock), resulting in a conditioned fear response. Fear memory retention is assessed thorough freezing behaviour, a species-specific defensive reaction, observed during exposure to the conditioned stimulus alone. Fear memory is influenced by sex and stress, with stress exposure prior to conditioning potentially inducing maladaptive fear responses. This meta-analysis examines how pre-conditioning stress exposure modulates memory retention in rodents. Across N = 94 studies included, we analyzed freezing behaviour based on several factors: type of paradigm (CFC vs AFC), species (rat vs mouse), sex (male vs female), stress type (physical vs pharmacological vs psychological vs combination of two or more stressors type), stress duration (acute or chronic), stress timing (prenatal vs early postnatal vs adolescence vs adulthood). The results indicate that stress significantly enhances contextual conditioned freezing behaviour. Stress-induced effects in CFC models vary across species but are not sex-specific. Additionally, these effects are influenced by stress-related factors. These findings highlight the importance of considering multiple variables when studying stress and fear memory processes, offering valuable insights for improving clinical approaches to fear memory-related diseases (e.g., post-traumatic stress disorder).
巴甫洛夫式恐惧条件反射是一种广泛用于研究啮齿动物恐惧记忆的行为任务。在条件反射过程中，啮齿动物学会将条件刺激（例如，环境或音调；分别为情境性或听觉性恐惧条件反射，CFC或AFC）与厌恶性刺激（例如，足部电击）联系起来，从而产生条件性恐惧反应。通过单独暴露于条件刺激期间观察到的僵住行为（一种物种特异性防御反应）来评估恐惧记忆的保持情况。恐惧记忆受性别和应激的影响，在条件反射之前暴露于应激可能会诱发适应不良的恐惧反应。这项荟萃分析研究了条件反射前的应激暴露如何调节啮齿动物的记忆保持。在所纳入的N = 94项研究中，我们基于几个因素分析了僵住行为：范式类型（CFC与AFC）、物种（大鼠与小鼠）、性别（雄性与雌性）、应激类型（物理性与药理学性与心理性与两种或更多种应激源类型的组合）、应激持续时间（急性或慢性）、应激时间（产前与产后早期与青春期与成年期）。结果表明，应激显著增强情境性条件性僵住行为。CFC模型中应激诱导的效应因物种而异，但无性别特异性。此外，这些效应受与应激相关的因素影响。这些发现突出了在研究应激和恐惧记忆过程时考虑多个变量的重要性，为改善与恐惧记忆相关疾病（例如，创伤后应激障碍）的临床方法提供了有价值的见解。
