Corticotropin releasing factor (CRF) modulates fear-induced alterations in sleep in mice

Brain Res. 2009 Jun 18:1276:112-22. doi: 10.1016/j.brainres.2009.04.017. Epub 2009 Apr 17.


Contextual fear significantly reduces rapid eye movement sleep (REM) during post-exposure sleep in mice and rats. Corticotropin releasing factor (CRF) plays a major role in CNS responses to stressors. We examined the influence of CRF and astressin (AST), a non-specific CRF antagonist, on sleep after contextual fear in BALB/c mice. Male mice were implanted with transmitters for recording sleep via telemetry and with a guide cannula aimed into the lateral ventricle. Recordings for vehicle and handling control were obtained after ICV microinjection of saline (SAL) followed by exposure to a novel chamber. Afterwards, the mice were subjected to shock training (20 trials, 0.5 mA, 0.5 s duration) for 2 sessions. After training, separate groups of mice received ICV microinjections of SAL (0.2 microl, n=9), CRF (0.4 microg, n=8), or AST (1.0 microg, n=8) prior to exposure to the shock context alone. Sleep was then recorded for 20 h (8-hour light and 12-hour dark period). Compared to handling control, contextual fear significantly decreased REM during the 8-h light period in mice receiving SAL and in mice receiving CRF, but not in the mice receiving AST. Mice receiving CRF exhibited reductions in REM during the 12-h dark period after contextual fear, whereas mice receiving SAL or AST did not. CRF also reduced non-REM (NREM) delta (slow wave) amplitude in the EEG. Only mice receiving SAL prior to contextual fear exhibited significant reductions in NREM and total sleep. These findings demonstrate a role for the central CRF system in regulating alterations in sleep induced by contextual fear.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain / drug effects
  • Brain / physiology
  • Catheterization
  • Conditioning, Classical
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / metabolism*
  • Darkness
  • Electrodes, Implanted
  • Electroencephalography
  • Electroshock
  • Environment
  • Fear*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microinjections
  • Peptide Fragments / administration & dosage
  • Sleep / drug effects
  • Sleep / physiology*
  • Sleep, REM / drug effects
  • Sleep, REM / physiology


  • Peptide Fragments
  • astressin
  • Corticotropin-Releasing Hormone