Role of cortisol, sleep, and glucocorticoid receptors in memory consolidation and retrieval

Abstract

Background : Memory functions involve three stages: encoding, consolidation, and retrieval. Modulating effects of glucocorticoids (GCs) have been consistently observed for encoding and retrieval. However, little is known on how GCs affect consolidation. Methods : In Study I, after encoding emotional and neutral texts, cortisol or placebo was intravenously infused while participants were either awake (N = 16) or napped (N=16). Study II and III investigate the mechanisms underlying the fact that memory retrieval is impaired at very low as well as very high cortisol levels but not at intermediate levels. Using specific receptor antagonists, we examined the role of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in memory retrieval. Using a double-blind within-subject, cross-over design, participants retrieved emotional and neutral material (learnt 3 days earlier) between 7:45 a.m. and 9:15 a.m. after administration of 400 mg of the MR blocker spironolactone vs. placebo (200 mg at 22:30 p.m. and 200mg at 4 a.m., Study II) or the GR blocker mifepristone vs. placebo (200 mg at 23:00 p.m., Study III). Results : In Study I, retention of temporal order within the texts was enhanced when cortisol was infused during the wake phase but impaired when it was infused during sleep. In Study II, blockade of MRs impaired free recall of both texts and pictures, especially for emotional material. In contrast, blockade of GRs resulted in better memory retrieval. Conclusions : Study I points toward fundamentally different mechanisms of cortisol on hippocampal memory consolidation, depending on the brain state. Study II and III indicate opposing roles of MRs and GRs in memory retrieval.

Keywords

• cortisol
• sleep
• glucocorticoid receptors
• memory consolidation
• retrieval