This study tested whether l-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg l-DOPA/carbidopa (n = 28), or 200/50 mg l-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of l-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that l-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.

这项研究测试了在恐惧消退学习后的巩固窗口期间交付的l- DOPA 是否会减少患有 PTSD 的女性随后的恐惧反应。被诊断患有 PTSD 的成年女性在 fMRI 期间完成了情境恐惧获取和消除任务，然后立即接受安慰剂（n  = 34）、100/25 mg l -DOPA/卡比多巴（n  = 28）或 200/50 mg l -DOPA /卡比多巴 ( n  = 29)。参与者在任务前完成静息状态扫描，并在药物摄入后 45 分钟再次完成扫描，以表征l的影响-DOPA 对巩固期间消退记忆神经再激活模式的影响。24 小时后，参与者返回进行功能磁共振成像期间的上下文更新、消退回忆和恢复测试，同时进行皮肤电导响应 (SCR) 评估。在任务后静息状态扫描期间，两个活性药物组都表现出杏仁核中消退编码的重新激活增加。对于 SCR 数据，与安慰剂相比，两个药物组在所有刺激中的第 2 天恢复均减少，并且有证据表明，与安慰剂相比，100 mg 组对恐惧刺激的上下文更新减少。对于成像数据，与安慰剂相比，两个药物组均显示双侧脑岛网络中刺激的第 2 天恢复减少。在 SCR 或神经活动中没有证据表明l -DOPA 提高了消光召回率。第 1 天巩固期间杏仁核中消退编码的重新激活预测了第 2 天岛叶网络的激活。这些结果支持巩固窗口期间多巴胺在促进 PTSD 女性杏仁核消退编码的重新激活和减少恢复但不改善消退回忆方面的作用。