Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.
Deutsches Resilienz Zentrum (DRZ), Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
Psychopharmacology (Berl). 2019 Dec;236(12):3401-3412. doi: 10.1007/s00213-019-05301-4. Epub 2019 Jun 26.
A promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction.
In two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session.
In both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction.
The results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.
在焦虑障碍的暴露疗法后，通过药理学增强假定发生的消退记忆巩固，是预防恐惧复发的一种有前景的策略。越来越多的证据表明，许多药理学巩固增强剂的效果取决于暴露过程中恐惧的成功减少。在这里，我们使用多巴胺前体 L-DOPA 来阐明其增强消退记忆巩固的潜在作用是否依赖于成功的恐惧消退。
在两个双盲、随机和安慰剂对照的实验（实验 1：N=79，实验 2：N=32）中，包括恐惧条件反射（第 1 天）、随后进行的消退，以及给予 150mg L-DOPA 或安慰剂（第 2 天）和记忆测试（第 3 天），在健康成年男性中，评估条件反应作为差异皮肤电导反应。我们测试了 L-DOPA 对测试时条件反应的影响是否取决于消退结束时的条件反应，在一个具有短（10 次试验，实验 1）和长（25 次试验，实验 2）消退的实验中进行了测试。
在两个实验中，L-DOPA 的作用都依赖于消退结束时的条件反应。也就是说，与安慰剂相比，消退后给予 L-DOPA 仅在消退结束时表现出完全消除条件恐惧的参与者中，降低了测试时的条件反应。
结果支持将 L-DOPA 作为暴露治疗的药理学辅助剂的潜在用途，但指出了药理学巩固增强剂的共同边界条件：暴露疗程中恐惧的成功减少。
