Continuous blockade of brain mineralocorticoid receptors impairs spatial learning in rats.

Hippocampal mineralocorticoid receptors (MR) are proposed to mediate facilitation of cognition in the short-term. The acute central blockade of MR increases 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 infused intracerebroventricularly (i.c.v.) (100 ng/h) via Alzet minipumps for 12 days. Rats given chronic i.c.v. infusion of spironolactone spent significantly less time (20% decrease, P < 0.05) within the platform quadrant during the watermaze probe test. Neither hippocampal MR nor glucocorticoid receptor mRNA expression were affected by spironolactone. Morning plasma corticosterone levels and adrenal and thymic weights were unchanged. Chronic central MR antagonism impairs spatial memory in the watermaze independent of changes in receptors or circulating glucocorticoid levels.