Continuous blockade of brain mineralocorticoid receptors impairs spatial learning in rats

Hippocampal mineralocorticoid receptors (MR) are proposed to mediate facili tation of cognition in the short-term. The acute central blockade of MR inc reases plasma corticosterone levels which itself can affect cognition thus complicating the interpretation of such studies. We therefore investigated the effects of chronic continuous central MR antagonism by spironolactone i nfused intracerebroventricularly (i.c.v.) (100 ng/h) via Alzet minipumps fo r 12 days. Rats given chronic i.c.v. infusion of spironolactone spent signi ficantly less time (20% decrease, P < 0.05) within the platform quadrant du ring the watermaze probe test. Neither hippocampal MR nor glucocorticoid re ceptor mRNA expression were affected by spironolactone. Morning plasma cort icosterone levels and adrenal and thymic weights were unchanged. Chronic ce ntral MR antagonism impairs spatial memory in the watermaze independent of changes in receptors or circulating glucocorticoid levels. (C) 1999 Elsevie r Science Ireland Ltd. All rights reserved.