Blocking mineralocorticoid receptors impairs, blocking glucocorticoid receptors enhances memory retrieval in humans.
Blocking mineralocorticoid receptors impairs, blocking glucocorticoid receptors enhances memory retrieval in humans.
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DOI：
10.1038/npp.2012.254
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发表时间：
2013-04
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--
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记忆提取在皮质醇水平很低和很高时都会受损，但在中等水平时则不会。皮质醇水平和记忆提取之间的这种倒U形关系可能源于盐皮质激素（MR）和糖皮质激素受体（GR）的不同作用，它们以明显不同的亲和力结合皮质醇。在这里，我们研究的作用，MR和GR在人类记忆检索使用特定的受体拮抗剂。在两项双盲的受试者内、交叉设计的研究中，年轻健康的男性被要求提取情感和中性的文本和图片（3天前获悉）早晨07：45至09：15之间，在给予400 mg MR阻滞剂螺内酯与安慰剂后（在2300小时200 mg和在0400小时200 mg，研究I）或在施用GR阻断剂米非司酮相对于安慰剂（在2300小时200 mg，研究II）之后。阻断MR会损害对文本和图片的自由回忆，尤其是对情感材料。与此相反，GRs的封锁导致更好的记忆检索的图片，效果更为明显的中性比情感材料。这些研究结果表明，MR和GR在记忆检索中确实具有相反的作用，最佳检索在中间皮质醇水平可能介导的高MR，但同时低GR激活。
Memory retrieval is impaired at very low as well as very high cortisol levels, but not at intermediate levels. This inverted-U-shaped relationship between cortisol levels and memory retrieval may originate from different roles of the mineralocorticoid (MR) and glucocorticoid receptor (GR) that bind cortisol with distinctly different affinity. Here, we examined the role of MRs and GRs in human memory retrieval using specific receptor antagonists. In two double-blind within-subject, cross-over designed studies, young healthy men were asked to retrieve emotional and neutral texts and pictures (learnt 3 days earlier) between 0745 and 0915 hours in the morning, either after administration of 400 mg of the MR blocker spironolactone vs placebo (200 mg at 2300 hours and 200 mg at 0400 hours, Study I) or after administration of the GR blocker mifepristone vs placebo (200 mg at 2300 hours, Study II). Blockade of MRs impaired free recall of both texts and pictures particularly for emotional material. In contrast, blockade of GRs resulted in better memory retrieval for pictures, with the effect being more pronounced for neutral than emotional materials. These findings indicate indeed opposing roles of MRs and GRs in memory retrieval, with optimal retrieval at intermediate cortisol levels likely mediated by high MR but concurrently low GR activation.
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