Effects of cortisol suppression on sleep-associated consolidation of neutral and emotional memory

Biol Psychiatry. 2005 Dec 1;58(11):885-93. doi: 10.1016/j.biopsych.2005.05.008. Epub 2005 Jul 7.


Background: Previous research indicates that hippocampus-dependent declarative memory benefits from early nocturnal sleep, when slow-wave sleep (SWS) prevails and cortisol release is minimal, whereas amygdala-dependent emotional memory is enhanced through late sleep, when rapid eye movement (REM) sleep predominates. The role of the strong cortisol rise accompanying late sleep for emotional memory consolidation has not yet been investigated.

Methods: Effects of the cortisol synthesis inhibitor metyrapone on sleep-associated consolidation of memory for neutral and emotional texts were investigated in a randomized, double-blind, placebo-controlled study in 14 healthy men. Learning took place immediately before treatment, which was followed by 8 hours of sleep. Retrieval was tested at 11 am the next morning.

Results: Metyrapone suppressed cortisol during sleep and blocked particularly the late-night rise in cortisol. It reduced SWS and concomitantly impaired the consolidation of neutral texts. Emotional texts were spared from this impairing influence, however. Metyrapone even amplified emotional enhancement in text recall indicating amygdala-dependent memory.

Conclusions: Cortisol blockade during sleep impairs hippocampus-dependent declarative memory formation but enhances amygdala-dependent emotional memory formation. The natural cortisol rise during late sleep may thus protect from overshooting emotional memory formation, a mechanism possibly pertinent to the development of posttraumatic stress disorder.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Affect / physiology
  • Attention / physiology
  • Cross-Over Studies
  • Double-Blind Method
  • Emotions / physiology*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrocortisone / antagonists & inhibitors*
  • Male
  • Memory / physiology*
  • Metyrapone / pharmacology
  • Norepinephrine / blood
  • Polysomnography
  • Sleep / physiology*
  • Sleep, REM / physiology


  • Enzyme Inhibitors
  • Adrenocorticotropic Hormone
  • Hydrocortisone
  • Norepinephrine
  • Metyrapone