Antagonizing corticotropin-releasing factor in the central nucleus of the amygdala attenuates fear-induced reductions in sleep but not freezing

Sleep. 2011 Nov 1;34(11):1539-49. doi: 10.5665/sleep.1394.


Study objectives: Contextual fear is followed by significant reductions in rapid eye movement sleep (REM) that are regulated by the central nucleus of the amygdala (CNA). Corticotropin-releasing factor (CRF) plays a major role in regulating the stress response as well as arousal, and CRF in CNA is implicated in stress-related behavior. To test the hypothesis that CRF regulation of CNA is involved in fear-induced alterations in REM, we determined the effects of microinjections into CNA of the CRF1 antagonist, antalarmin (ANT) on fear-induced reductions in REM. We also evaluated c-Fos activation in the hypothalamic paraventricular nucleus (PVN), locus coeruleus (LC), and dorsal raphe nucleus (DRN) to determine whether activation of these regions was consistent with their roles in regulating stress and in the control of REM.

Design: On separate days, rats were subjected to baseline and 2 shock training sessions (S1 and S2). Five days later, the rats received bilateral microinjections of ANT (4.8 mM) or vehicle (VEH) prior to exposure to the fearful context. Sleep was recorded for 20 h in each condition. Freezing was assessed during S1, S2, and context. Separate groups of rats received identical training and microinjections or handling control (HC) only, but were sacrificed 2 h after context exposure to assess c-Fos expression.

Setting: NA.

Patients or participants: NA.

Interventions: NA.

Measurements and results: Compared to baseline, S1 and S2 significantly reduced REM. Exposure to the fearful context reduced REM in VEH treated rats, whereas REM in ANT treated rats did not differ from baseline. ANT did not significantly alter freezing. Fear-induced c-Fos expression was decreased in PVN and LC after ANT compared to VEH.

Conclusions: The results demonstrate that CRF receptors in CNA are involved in fear-induced reductions in REM and neural activation (as indicated by c-Fos) in stress and REM regulatory regions, but not in fear-induced freezing.

Keywords: Central nucleus of the amygdala; contextual fear; corticotropin releasing factor; dorsal raphe nucleus; locus coeruleus; paraventricular nucleus.

Publication types

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

MeSH terms

  • Amygdala / chemistry
  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Corticotropin-Releasing Hormone / physiology
  • Electrodes, Implanted
  • Electroencephalography
  • Electromyography
  • Fear / physiology*
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology
  • Male
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / physiology
  • Pyrimidines / pharmacology*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Wistar
  • Sleep / drug effects*
  • Sleep / physiology
  • Sleep, REM / drug effects
  • Sleep, REM / physiology


  • Proto-Oncogene Proteins c-fos
  • Pyrimidines
  • Pyrroles
  • antalarmin
  • Corticotropin-Releasing Hormone