Kindt Merel, Soeter Marieke, Sevenster Dieuwke
Department of Clinical Psychology, University of Amsterdam;
Department of Clinical Psychology, University of Amsterdam.
J Vis Exp. 2014 Dec 18(94):52151. doi: 10.3791/52151.
The basic design used in our human fear-conditioning studies on disrupting reconsolidation includes testing over different phases across three consecutive days. On day 1 - the fear acquisition phase, healthy participants are exposed to a series of picture presentations. One picture stimulus (CS1+) is repeatedly paired with an aversive electric stimulus (US), resulting in the acquisition of a fear association, whereas another picture stimulus (CS2-) is never followed by an US. On day 2 - the memory reactivation phase, the participants are re-exposed to the conditioned stimulus without the US (CS1-), which typically triggers a conditioned fear response. After the memory reactivation we administer an oral dose of 40 mg of propranolol HCl, a β-adrenergic receptor antagonist that indirectly targets the protein synthesis required for reconsolidation by inhibiting the noradrenaline-stimulated CREB phosphorylation. On day 3 - the test phase, the participants are again exposed to the unreinforced conditioned stimuli (CS1- and CS2-) in order to measure the fear-reducing effect of the manipulation. This retention test is followed by an extinction procedure and the presentation of situational triggers to test for the return of fear. Potentiation of the eye blink startle reflex is measured as an index for conditioned fear responding. Declarative knowledge of the fear association is measured through online US expectancy ratings during each CS presentation. In contrast to extinction learning, disrupting reconsolidation targets the original fear memory thereby preventing the return of fear. Although the clinical applications are still in their infancy, disrupting reconsolidation of fear memory seems to be a promising new technique with the prospect to persistently dampen the expression of fear memory in patients suffering from anxiety disorders and other psychiatric disorders.
我们在人类恐惧条件反射研究中用于破坏重新巩固的基本设计包括在连续三天的不同阶段进行测试。在第1天——恐惧习得阶段，健康参与者会接触一系列图片展示。一种图片刺激（CS1+）会反复与厌恶电刺激（US）配对，从而形成恐惧关联，而另一种图片刺激（CS2-）之后从不跟随US。在第2天——记忆重新激活阶段，参与者在没有US的情况下再次接触条件刺激（CS1-），这通常会引发条件性恐惧反应。在记忆重新激活后，我们口服一剂40毫克的盐酸普萘洛尔，这是一种β-肾上腺素能受体拮抗剂，通过抑制去甲肾上腺素刺激的CREB磷酸化间接靶向重新巩固所需的蛋白质合成。在第3天——测试阶段，参与者再次接触未强化的条件刺激（CS1-和CS2-），以测量操作的恐惧减轻效果。这个保持测试之后是一个消退程序，并呈现情境触发因素以测试恐惧的恢复。眨眼惊跳反射的增强被测量作为条件性恐惧反应的指标。通过在每次CS呈现期间的在线US预期评分来测量对恐惧关联的陈述性知识。与消退学习不同，破坏重新巩固针对原始恐惧记忆，从而防止恐惧的恢复。尽管临床应用仍处于起步阶段，但破坏恐惧记忆的重新巩固似乎是一种有前途的新技术，有望持续抑制患有焦虑症和其他精神疾病患者的恐惧记忆表达。
