Department of Clinical Psychology, University of Amsterdam, 1018 WB Amsterdam, The Netherlands.
Learn Mem. 2011 May 16;18(6):357-66. doi: 10.1101/lm.2148511. Print 2011 Jun.
We previously demonstrated that disrupting reconsolidation by pharmacological manipulations "deleted" the emotional expression of a fear memory in humans. If we are to target reconsolidation in patients with anxiety disorders, the disruption of reconsolidation should produce content-limited modifications. At the same time, the fear-erasing effects should not be restricted to the feared cue itself considering that fear generalization is a main characteristic of anxiety disorders. In Experiment I and Experiment I(b), we addressed these issues using a within-subject differential startle fear conditioning paradigm and a test of fear generalization. In Experiment II, we tested whether a behavioral approach targeting the reconsolidation through extinction learning was also effective in weakening the original fear memory. A behavioral procedure is evidently preferred over drug manipulations provided that similar effects can be obtained. Here, the extinction procedure subsequent to retrieval did not "erase" the emotional expression of the fear memory as the retrieval techniques (i.e., reminder shocks and reacquisition) unveiled a return of the startle fear response to the fear-relevant stimuli. In contrast, β-adrenergic receptor blockade during reconsolidation selectively deleted the fear-arousing aspects of the memory (i.e., startle fear response) along with its category-related information. The pharmacological manipulation rendered the core memory trace too weak to observe fear generalization after successful reacquisition. Hence, relearning following the disruption of reconsolidation seems to be qualitatively different from initial learning. Our findings demonstrate that disrupting reconsolidation by pharmacological manipulations, although selective, undermines the generalization of fear, a key feature of anxiety disorders.
我们之前的研究表明，通过药理学手段干扰再巩固过程可以“删除”人类恐惧记忆的情绪表达。如果我们要针对焦虑障碍患者的再巩固过程进行靶向治疗，那么再巩固的干扰应该只产生内容受限的改变。同时，鉴于恐惧泛化是焦虑障碍的主要特征，这种消除恐惧的效果不应仅限于恐惧线索本身。在实验 1 和实验 1(b)中，我们使用了一种基于个体差异的起始惊吓恐惧条件反射范式和恐惧泛化测试来解决这些问题。在实验 2 中，我们测试了针对再巩固的行为趋近通过消退学习是否也能有效削弱原始的恐惧记忆。只要能获得类似的效果，行为程序显然优于药物操作。在这里，检索后进行的消退程序并没有“消除”恐惧记忆的情绪表达，因为检索技术（即提醒性电击和重新获得）揭示了起始惊吓反应重新回到与恐惧相关的刺激。相比之下，再巩固过程中β-肾上腺素能受体阻断选择性地删除了记忆的引起恐惧的方面（即起始惊吓反应）及其与类别相关的信息。这种药理学操作使核心记忆痕迹变得非常微弱，以至于在成功重新获得后无法观察到恐惧泛化。因此，再巩固干扰后的重新学习似乎在质上与初始学习不同。我们的研究结果表明，通过药理学手段干扰再巩固过程虽然具有选择性，但会破坏恐惧的泛化，而恐惧的泛化是焦虑障碍的一个关键特征。
