P.1.e.017 A decrease in phosphorylation of CREB may explain delayed place learning and attenuated long-term potentiation in adult-onset hyperthyroidism

Abstract

The hippocampal mineralocorticoid receptor (MR) is critical for the regulation of the basal activity of the hypothalamus–pituitary–adrenocortical (HPA) system. It has been hypothesized that reduced capacity of the hippocampal MR is involved in the HPA-system dysregulation found in depression and aging. We applied the combined dexamethasone suppression/corticotropin releasing hormone stimulation (DEX/CRH) test to six healthy young females both before and after 12 days of treatment with the MR antagonist spironolactone to assess HPA regulation. Treatment with spironolactone caused a significant increase in post-dexamethasone cortisol concentrations (75.1±56.7 vs. 36.6±24.6 nmol/l, p<0.05). Furthermore, we observed a significant rise in peak cortisol concentration after additional human CRH (hCRH) application (223.6±139.1 vs. 126.7±73.3 nmol/l, p<0.02). There was no change in ACTH plasma concentrations. We thus conclude that (1) the MR antagonist spironolactone affects HPA system regulation as reflected in the DEX/CRH test and (2) these findings are in accordance with the assumption that MR dysfunction may underlie HPA-system dysfunction in depression and/or aging.