REPEATED BLOCKADE OF MINERALOCORTICOID RECEPTORS, BUT NOT OF GLUCOCORTICOID RECEPTORS IMPAIRS FOOD REWARDED SPATIAL-LEARNING

Corticosteroids from the adrenal cortex influence a variety of behavio urs including cognition, learning and memory. These hormones act via t wo intracellular receptors, the mineralo-corticoid receptor (MR) and t he glucocorticoid receptor (GR). These two receptor types display a hi gh concentration and distinct distribution in the hippocampus, a brain region which is directly involved in the regulation of spatial orient ation and learning. In this study, repeated subcutaneous administratio n of the mineralocorticoid receptor antagonist RU28318 (1.0 mg/100 g b ody weight), the glucocorticoid receptor blocker RU38486 (2.5 mg/100 g body weight), or a combination of both antagonists were investigated for their effects on working-and reference memory in morning and after noon trials during 8 subsequent days in food rewarded spatial learning in a hole board task. Each rat received one dose of either vehicle (2 % ethanol in PEG 400), RU28318, RU38486 or the combination of both ant agonists directly after the first trial on training days 1, 3, 5, and 7. The experiments demonstrated that repeated blockade of mineralocort icoid receptors impairs reference memory reflected in the morning-as w ell as in the afternoon trial, whereas blockade of glucocorticoid rece ptors has little effect on this type of cognitive behaviour. Furthermo re, combined blockade of MRs and GRs resulted in a decrease, in both d aily trials, in reference memory as well as working memory performance . These findings suggest that in this spatial learning paradigm, the i mpairment of working memory required blockade of both receptor types, while reference memory performance involves predominantly the mineralo corticoid receptors. (C) 1998 Elsevier Science Ltd. All rights reserve d.