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Continuous blockade of brain mineralocorticoid receptors impairs spatial learning in rats
1Molecular Endocrinology Laboratory, Molecular Medicine Centre, Western General Hospital, Edinburgh, Scotland, UK. joyce.yau@ed.ac.uk
Abstract:
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.
Insights
Chronic central mineralocorticoid receptor (MR) antagonism in rats impaired spatial memory. This effect occurred independently of changes in MR or glucocorticoid receptor mRNA, or circulating glucocorticoid levels.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- Hippocampal mineralocorticoid receptors (MR) are implicated in short-term cognitive facilitation.
- Acute central MR blockade confounds cognitive studies by altering plasma corticosterone.
Purpose of the Study:
- To investigate the effects of chronic central MR antagonism on spatial memory.
- To determine if chronic MR antagonism impacts hippocampal receptor expression or corticosterone levels.
Main Methods:
- Rats received chronic intracerebroventricular (i.c.v.) infusion of spironolactone (100 ng/h) for 12 days.
- Spatial memory was assessed using a watermaze probe test.
- Hippocampal MR and glucocorticoid receptor mRNA expression, plasma corticosterone, and organ weights were analyzed.
Main Results:
- Chronic central MR antagonism significantly reduced time spent in the platform quadrant during the watermaze probe test (20% decrease, P < 0.05).
- No significant changes were observed in hippocampal MR or glucocorticoid receptor mRNA expression.
- Morning plasma corticosterone levels and adrenal and thymic weights remained unchanged.
Conclusions:
- Chronic central mineralocorticoid receptor antagonism impairs spatial memory in rats.
- This impairment is independent of alterations in hippocampal receptor mRNA expression or circulating glucocorticoid levels.