Sex differences in mouse models of fear inhibition: Fear extinction, safety learning, and fear-safety discrimination
Sex differences in mouse models of fear inhibition: Fear extinction, safety learning, and fear-safety discrimination
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DOI：
10.1111/bph.14600
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发表时间：
2019-11-01
影响因子：
7.3
通讯作者：
Jacobson, Laura H.
中科院分区：
文献类型：
--
作者：
Clark, Jacob W.;Drummond, Sean P. A.;Jacobson, Laura H.
背景和目的女性在创伤后应激障碍(PTSD)中的比例过高，这是一种以对恐惧的无效抑制为特征的精神障碍。雄性动物的使用在临床前研究中占据主导地位，这可能导致对这种差异存在的原因缺乏理解。因此，目前的研究探索了三种恐惧抑制小鼠模型的性别差异。实验方法所有实验均以雄性和雌性C57BL/6J小鼠为测试对象。实验一采用了两种恐惧条件反射方案，其中音调与不同强度(中等或强烈)的足部电击配对。随后对恐惧、回忆和消退进行了测试。实验二对安全学习进行了考察。在安全条件反射期间，音调明显与脚部电击不成对。24小时后进行安全学习回忆测试。实验3评估了一个恐惧-安全歧视模型。在恐惧和安全条件反射中，线索刺激分别与足部电击配对或从未配对。24小时后评估刺激物之间的辨别能力。恐惧消退的关键结果是，与女性相比，男性在最接近条件反射的阶段表现出更大的恐惧，但随后随着时间的推移，恐惧消失得更快。安全学习过程中未观察到性别差异。在恐惧-安全辨别中，男性和女性都对刺激进行了区分；然而，男性对刺激表现出了更高的冷漠程度。结论和启示本研究提供的证据表明，性别差异影响C57BL/6J小鼠的恐惧行为，但不影响基于安全的行为。这些发现表明，处理恐惧，而不是安全，可能在创伤后应激障碍的性别差异中发挥更大的作用。链接文章这篇文章是关于药理学研究中性别差异的重要性的主题部分的一部分。要查看本节中的其他文章，请访问
Background and Purpose Women are overrepresented in post-traumatic stress disorder (PTSD), a mental disorder characterised by ineffective inhibition of fear. The use of male animals dominates preclinical studies, which may contribute to a lack of understanding as to why this disparity exists. Thus, the current study explores sex differences in three mouse models of fear inhibition. Experimental Approach All experiments tested male and female C57Bl/6J mice. Experiment 1 employed two fear conditioning protocols, in which tones were paired with footshocks of differing intensity (moderate or intense). Fear recall and extinction were tested subsequently. In Experiment 2, safety learning was investigated. Tones were explicitly unpaired with footshocks during safety conditioning. Recall of safety learning was tested 24 hr later. Experiment 3 assessed a model of fear-safety discrimination. Cued stimuli were paired or never paired with footshocks during fear and safety conditioning, respectively. Discrimination between stimuli was assessed 24 hr later. Key Results In fear extinction, males, compared to females, responded with greater fear in sessions most proximal to conditioning but subsequently showed a more rapid fear extinction over time. Sex differences were not observed during safety learning. During fear-safety discrimination, both males and females discriminated between stimuli; however, males revealed a greater level of freezing to stimuli. Conclusion and Implications The current study provides evidence that sex differences influence fear but not safety-based behaviour in C57Bl/6J mice. These findings indicate that processing of fear, but not safety, may play a greater role in sex differences observed for PTSD. LINKED ARTICLES This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit