Mineralocorticoid and glucocorticoid receptors and their differential effects on memory performance in people with Addison's disease.

The effects of corticosteroids on memory performance have been the subject of some controversy. Whilst many studies have shown that high levels of corticosteroids can impair memory performance, others have shown they can facilitate it. One explanation for these discrepant effects arises from the differential activation of the two types of corticosteroid receptor--the mineralocorticoid receptor (MRs) and the glucocorticoid receptor (GRs), and the function each subserves during memory formation. Studies in rats and chickens suggest that activation of the MRs is essential during sensory storage (i.e. encoding), whereas normal levels of activation of the GRs (in addition to the already activated MRs) is essential during memory consolidation and retrieval. By using a repeated measures design with nine people with Addison's disease (mean age, 37.9 years), the effects following activation of the MRs only, GRs only, and a combination of MRs/GRs, on working memory and the episodic and semantic components of declarative memory were investigated. MRs and GRs were activated using either MR specific (9 alpha fluorohydrocortisone) or GR specific (dexamethasone) exogenous steroids, respectively. The results showed that participants performed better in the Digits Backward task when both receptors were activated compared to when GRs only were activated (P<0.01). They also performed better in recall in the Hopkins Verbal Learning Test when both receptors were activated compared to when MRs only were activated (P<0.05) and GRs only were activated (P<0.01). Whilst significant effects were not consistent across memory tasks, these results lend further support to the view that balanced activation of MRs and GRs is necessary for optimal memory function in humans.