Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Neuropsychopharmacology. 2011 Dec;36(13):2720-8. doi: 10.1038/npp.2011.162. Epub 2011 Aug 31.
Corticosteroids, released in high amounts after stress, exert their effects via two different receptors in the brain: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). GRs have a role in normalizing stress-induced effects and promoting consolidation, while MRs are thought to be important in determining the threshold for activation of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the effects of MR blockade on HPA axis responses to stress and stress-induced changes in cognitive function. In a double-blind, placebo-controlled study, 64 healthy young men received 400 mg of the MR antagonist spironolactone or placebo. After 1.5 h, they were exposed to either a Trier Social Stress Test or a non-stressful control task. Responses to stress were evaluated by hormonal, subjective, and physiological measurements. Afterwards, selective attention, working memory, and long-term memory performance were assessed. Spironolactone increased basal salivary cortisol levels as well as cortisol levels in response to stress. Furthermore, spironolactone significantly impaired selective attention, but only in the control group. The stress group receiving spironolactone showed impaired working memory performance. By contrast, long-term memory was enhanced in this group. These data support a role of MRs in the regulation of the HPA axis under basal conditions as well as in response to stress. The increased availability of cortisol after spironolactone treatment implies enhanced GR activation, which, in combination with MR blockade, presumably resulted in a decreased MR/GR activation ratio. This condition influences both selective attention and performance in various memory tasks.
皮质类固醇在应激后大量释放，通过大脑中的两种不同受体发挥作用：糖皮质激素受体 (GRs) 和盐皮质激素受体 (MRs)。GRs 在使应激诱导的效应正常化和促进巩固方面发挥作用，而 MRs 被认为在确定下丘脑-垂体-肾上腺 (HPA) 轴的激活阈值方面很重要。我们研究了 MR 阻断对 HPA 轴对应激的反应以及应激引起的认知功能变化的影响。在一项双盲、安慰剂对照研究中，64 名健康年轻男性接受了 400 毫克的 MR 拮抗剂螺内酯或安慰剂。1.5 小时后，他们接受了特里尔社会应激测试或非应激对照任务。通过激素、主观和生理测量来评估应激反应。之后，评估了选择性注意、工作记忆和长期记忆表现。螺内酯增加了基础唾液皮质醇水平以及应激时的皮质醇水平。此外，螺内酯显著损害了选择性注意力，但仅在对照组中。接受螺内酯的应激组显示出工作记忆表现受损。相比之下，该组的长期记忆得到增强。这些数据支持 MR 在基础条件下以及对应激的 HPA 轴调节中的作用。螺内酯治疗后皮质醇的可用性增加意味着 GR 激活增强，这与 MR 阻断相结合，可能导致 MR/GR 激活比率降低。这种情况会影响各种记忆任务中的选择性注意力和表现。
