Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA.
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA; Department of Medicine, University of Colorado Denver School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
Physiol Behav. 2019 Feb 1;199:343-350. doi: 10.1016/j.physbeh.2018.12.007. Epub 2018 Dec 4.
Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder (PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.
临床试验表明，3,4-亚甲二氧基甲基苯丙胺（MDMA）与心理疗法联合使用，比单独使用心理疗法或药物治疗更能有效减轻创伤后应激障碍（PTSD）的症状。MDMA 增强心理疗法效果的作用机制尚不清楚。鉴于恐惧记忆是 PTSD 症状的原因之一，MDMA 可以通过靶向恐惧记忆来增强心理疗法。本研究旨在探讨单次 MDMA 给药对成年雄性长耳大白鼠条件性恐惧记忆的消退和再巩固的影响。大白鼠经历了条件性的听觉或环境恐惧条件反射，然后系统地接受生理盐水或不同剂量的 MDMA（1 到 10mg/kg）的治疗，治疗时间分别为：在恐惧消退训练前 30 分钟或在短暂的恐惧记忆检索后（即再巩固阶段）。在恐惧消退训练前给予 MDMA 并没有增强恐惧消退记忆，实际上反而损害了无药物依赖的条件性恐惧消退记忆，而对后来的恐惧复发没有影响。在再巩固阶段给予 MDMA，但不在再巩固阶段之外给予，会导致条件性恐惧的延迟和持续减少。这些发现与 MDMA 对记忆的普遍破坏作用一致，并表明 MDMA 可以通过在再巩固过程中改变恐惧记忆来增强心理疗法，而不一定增强其消退。
