Department of Clinical Psychology, University of Amsterdam, Weesperplein 4, 1018 XA Amsterdam, The Netherlands.
Psychoneuroendocrinology. 2012 Nov;37(11):1769-79. doi: 10.1016/j.psyneuen.2012.03.011. Epub 2012 Apr 12.
Although memory for emotionally arousing and stressful experiences is strong and resistant to change, recent years have witnessed rapidly emerging evidence for the plasticity of fear memories. Upon retrieval a memory may be rendered labile and vulnerable to the disruptive effects of amnestic agents. This process is referred to as "disrupting reconsolidation" and may point to a novel therapeutic strategy for the permanent reduction of fear in patients suffering from anxiety disorders. However, the fear-reducing effects are thus far only demonstrated for freezing reactions in rodents and autonomic fear responding in humans. If disrupting reconsolidation will be of value for clinical practice, it should also target the subjective feelings of anxiety. Using an instructed fear-learning paradigm in humans, we here tested whether disrupting reconsolidation would diminish the subjective feelings of anxiety for a noxious event that was anticipated but never actually experienced. Beta-adrenergic receptor blockade during reconsolidation strongly diminished the behavioral expression of the instructed fear memory (i.e., startle responding) as well as the subjective feelings of anxiety 24h later, yet without affecting both the physiological and cognitive component of the anticipation of threat (i.e., skin conductance responding, expectancy ratings). Together, the present findings suggest that the various memory traces of a learned fear association do not necessarily undergo reconsolidation in harmony. Considering that patients with anxiety disorders (1) often fear objects and situations that they have never actually experienced, and (2) primarily suffer from the subjective feelings of anxiety, the present findings may have important ramifications for psychotherapy.
尽管对情绪唤起和压力体验的记忆是强烈的，并且难以改变，但近年来，恐惧记忆的可塑性的证据迅速涌现。在检索时，记忆可能变得不稳定，并容易受到遗忘剂的破坏作用的影响。这个过程被称为“破坏再巩固”，可能指向一种新的治疗策略，用于永久性地减少患有焦虑症的患者的恐惧。然而，到目前为止，这种恐惧减少的效果仅在啮齿动物的冻结反应和人类的自主恐惧反应中得到了证明。如果破坏再巩固将对临床实践有价值，那么它还应该针对焦虑的主观感受。在这里，我们使用人类的指令性恐惧学习范式来测试，在预期但从未实际经历过的有害事件中，破坏再巩固是否会减少焦虑的主观感受。在再巩固期间，β-肾上腺素能受体阻断强烈地减少了指令性恐惧记忆的行为表达（即，惊跳反应），以及 24 小时后焦虑的主观感受，而不会影响威胁预期的生理和认知成分（即，皮肤电反应、预期评分）。总之，目前的研究结果表明，习得性恐惧关联的各种记忆痕迹不一定协调地经历再巩固。考虑到焦虑症患者（1）经常害怕他们从未实际经历过的物体和情况，以及（2）主要遭受焦虑的主观感受，这些发现可能对心理治疗具有重要意义。
