Effects of mineralo-corticoid receptor modulation by spironolactone and fludrocortisone on cortisol secretion and learning performance under a stressful learning task

The activity of hypothalamus-hypophysis-adrenal (HPA) axis is regulated by mineralo- (MR) and glucocorticoid receptors. Animal studies suggest that the glucocorticoid- and the MR-system are involved in learning and memory. Therefore, we conducted a study to evaluate the effects of a modulation of the MR-System on basal and stress induced cortisol secretion and on learning and memory function. In an intraindividual placebo controlled completely balanced repeated measurement design 24 healthy male subjects received a single oral dosage of either 200mg spironolactone (SP), 0.1mg fludrocortisone (FL) or placebo (PL) three hours before a stressful learning task. Number of trials, correct and false answers during the learning task and the number of correctly recalled associations at the end of the experiment were assessed. Cortisol samples were obtained from saliva before and until 120min. after the beginning of the stress task. The application of 200mg SP significantly increased baseline cortisol secretion compared to PL and FL. After the application of SP cortisol secretion under stress was prolonged compared to FL. In addition, there was a trend for a better learning performance under FL. Spironolactone is able to increase the basal activity of the HPA-axis and may prolong stress induced cortisol secretion. A faster learning performance under FL compared to SP suggests that the modulation of the MR-function is related to learning performance probably mediated by cortisol.