Preextinction Stress Prevents Context-Related Renewal of Fear
Preextinction Stress Prevents Context-Related Renewal of Fear
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DOI：
10.1016/j.beth.2018.03.001
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发表时间：
2018-11-01
期刊：
影响因子：
3.7
通讯作者：
Wolf, Oliver T.
中科院分区：
文献类型：
--
作者：
Drexler, Shira Meir;Merz, Christian J.;Wolf, Oliver T.
灭绝学习创造了新的安全关联，被认为是暴露疗法的潜在机制，通常用于治疗焦虑症和创伤后应激障碍。恐惧记忆和安全记忆的相对强度和可提取性决定了在给定情况下的反应。虽然恐惧记忆通常与情境无关，并且很容易概括，但灭绝记忆具有高度的情境特异性。因此，在环境发生变化后，被消除的恐惧记忆可能会“再生”。目前的工作的目的是创建一个增强的和广义的灭绝记忆的离散刺激前灭绝学习的压力暴露，从而防止更新。在我们的情境恐惧条件化范式中，40名健康男性获得（第1天），检索和熄灭（第2天）的恐惧记忆，压力组和对照组之间没有差异。在更新试验（第3天）中，组间出现显著差异。在对照组（N = 20）中观察到更新效应，证实了消退记忆的上下文依赖性。相反，应激组（N = 20）没有显示更新效果。恐惧减少也被推广到习得情境，这表明压力使灭绝记忆更加独立于情境。这些结果与先前的研究一致，这些研究表明，由于学习前的压力，由糖皮质激素对海马体的快速作用介导的情境化中断。我们的研究结果支持了在暴露治疗中使用糖皮质激素或应激诱导的研究，并建议了正确的给药时机，以优化其效果。
Extinction learning, which creates new safety associations, is thought to be the mechanism underlying exposure therapy, commonly used for the treatment of anxiety disorders and posttraumatic stress disorder. The relative strength and availability for retrieval of both the fear and safety memories determine the response in a given situation. While the fear memory is often context-independent and may easily generalize, extinction memory is highly context-specific. "Renewal" of the extinguished fear memory might thus occur following a shift in context. The aim of the current work was to create an enhanced and generalized extinction memory to a discrete stimulus using stress exposure before extinction learning, thereby preventing renewal. In our contextual fear conditioning paradigm, 40 healthy men acquired (Day 1), retrieved and extinguished (Day 2) the fear memories, with no differences between the stress and the control group. A significant difference between the groups emerged in the renewal test (Day 3). A renewal effect was seen in the control group (N = 20), confirming the context-dependency of the extinction memory. In contrast, the stress group (N = 20) showed no renewal effect. Fear reduction was generalized to the acquisition context as well, suggesting that stress rendered the extinction memory more context-independent. These results are in line with previous studies that showed contextualization disruption as a result of pre-learning stress, mediated by the rapid effects of glucocorticoids on the hippocampus. Our findings support research investigating the use of glucocorticoids or stress induction in exposure therapy and suggest the right timing of administration in order to optimize their effects.