3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats
3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats
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DOI：
10.1016/j.physbeh.2018.12.007
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发表时间：
2019-02-01
影响因子：
2.9
通讯作者：
Greenwood, Benjamin N.
中科院分区：
文献类型：
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作者：
Hake, Holly S.;Davis, Jazmyne K. P.;Greenwood, Benjamin N.
临床试验表明，3，4-亚甲二氧基甲基苯丙胺（MDMA）与心理治疗相结合，比心理治疗或药物治疗更有效地减轻创伤后应激障碍（PTSD）的症状，单独或联合使用。MDMA增强心理治疗的过程还不太清楚。考虑到恐惧记忆有助于PTSD神经病学，MDMA可以通过针对恐惧记忆来增强心理治疗。目前的研究调查了单次给予MDMA对成年雄性Long-Evans大鼠线索和背景恐惧记忆消退和再巩固的影响。大鼠暴露于上下文或听觉恐惧条件反射，然后全身给予生理盐水或不同剂量的MDMA（1和10毫克/公斤之间）之前30分钟的恐惧消退训练或后立即短暂的恐惧记忆检索（即在重新巩固阶段）。在恐惧消退训练之前给予MDMA未能增强恐惧消退记忆，实际上损害了无药物提示的恐惧消退回忆，而不影响后来的恐惧复发。在再巩固阶段给予MDMA，但在再巩固阶段之外，产生了延迟和持续的条件性恐惧减少。这些发现与MDMA的一般记忆破坏作用一致，并表明MDMA可以通过在重新巩固期间修改恐惧记忆来增强心理治疗，而不一定会增强其消退。
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 re consolidation 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.