Spironolactone and low-dose dexamethasone enhance extinction of contextual fear conditioning

Abstract

Glucocorticoids play a role in memory formation, and they may contribute to memory changes in stress-related mental disorders, such as posttraumatic stress disorder. Cortisol may act through mineralocorticoid (MR) or glucocorticoid (GR) receptors, and the objective of the present study was to evaluate the effects of the MR antagonist spironolactone, the GR antagonist mifepristone, the MR agonist fludrocortisone, and the GR agonist dexamethasone on the extinction of contextually conditioned fear in rats. Propranolol was used as a positive control. As expected, propranolol administered before the test session increased memory extinction. Pre-test administration of spironolactone and low-dose dexamethasone also increased the extinction of an aversive memory, whereas fludrocortisone impaired extinction. High-dose dexamethasone and mifepristone were found to have no effect in this model. Post-test spironolactone treatment impaired aversive memory extinction. These results indicate that MR and GR are related to extinction of aversive memories, and MR blockade may be a promising candidate for the treatment of stress-related memory disorders.