Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia.
Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia.
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DOI：
10.1176/appi.ajp.2014.13101407
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Gonzalez-Lima F
中科院分区：
文献类型：
--
作者：
Telch MJ;Bruchey AK;Rosenfield D;Cobb AR;Smits J;Pahl S;Gonzalez-Lima F
临床前研究表明，低剂量的USP亚甲基蓝可以增加大脑中线粒体细胞色素氧化酶的活性，提高学习任务后的记忆力，包括消除恐惧。我们报告了第一个对照实验，以检验训练后亚甲基蓝对恐惧消退训练后恐惧消退和情境记忆保留的记忆增强效果。表现出明显幽闭恐惧的成年人（N = 42）被随机分为双盲组，分别服用260毫克亚甲基蓝和安慰剂，随后在一个封闭的房间进行6次5分钟的消失试验。一个月后进行了重新测试，以评估在暴露于未经训练的封闭室内时的恐惧峰值，并预测亚甲基蓝的效果将随着灭绝训练期间恐惧减少的功能而变化。在训练后1天和30天评估偶然情境记忆，以评估亚甲蓝的认知增强效果，而不依赖于其对恐惧衰减的影响。与预测一致，与安慰剂相比，在训练后接受亚甲基蓝治疗的参与者在训练后表现出低水平的恐惧，在随访中表现出明显更少的恐惧。相比之下，表现出中度至高度训练后恐惧的参与者在随访时的表现往往比安慰剂更差。亚甲基蓝对情境记忆的增强与最初或训练后的幽闭恐惧症恐惧无关。亚甲基蓝在一次成功的暴露后可以增强记忆和恐惧消退的保留，但在一次不成功的暴露后可能会对消退产生有害影响。
Preclinical studies have shown that low-dose USP methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. We report on the first controlled experiment to examine the memory-enhancing effects of post-training methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Adults (N = 42) displaying marked claustrophobic fear were randomized to double-blind administration of 260 mg of methylene blue versus placebo immediately following six five-minute extinction trials to an enclosed chamber. Retesting occurred one month later to assess fear renewal as indexed by peak fear during exposure to a non-trained enclosed chamber with the prediction that methylene blue's effects would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive enhancing effects of methylene blue independent of its effects on fear attenuation. Consistent with predictions, participants displaying low end fear at post-training showed significantly less fear at follow-up if they received methylene blue post-training relative to placebo. In contrast, participants displaying moderate to high levels of post-training fear tended to fare worse at follow-up relative to placebo. Methylene blue's enhancement of contextual memory was unrelated to initial or post-training claustrophobic fear. Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session, but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.
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