Antagonism of corticotropin releasing factor in the basolateral amygdala of resilient and vulnerable rats: Effects on fear-conditioned sleep, temperature and freezing

Horm Behav. 2018 Apr:100:20-28. doi: 10.1016/j.yhbeh.2018.02.013. Epub 2018 Mar 12.


The basolateral nucleus of the amygdala (BLA) plays a significant role in mediating individual differences in the effects of fear memory on sleep. Here, we assessed the effects of antagonizing corticotropin releasing factor receptor 1 (CRFR1) after shock training (ST) on fear-conditioned behaviors and sleep. Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and with bilateral guide cannulae directed at BLA. Data loggers were placed intraperitoneally to record core body temperature. The CRFR1 antagonist, antalarmin (ANT; 4.82 mM) was microinjected into BLA after shock training (ST: 20 footshocks, 0.8 mA, 0.5 s duration, 60 s interstimulus interval), and the effects on sleep, freezing and the stress response (stress-induced hyperthermia, SIH) were examined after ST and fearful context re-exposure alone at 7 days (CTX1) and 21 days (CTX2) post-ST. EEG and EMG recordings were scored for non-rapid eye movement sleep (NREM), rapid eye movement sleep (REM) and wakefulness. The rats were separated into 4 groups: Vehicle-vulnerable (Veh-Vul; n = 10), Veh-resilient (Veh-Res; n = 11), ANT-vulnerable (ANT-Vul; n = 8) and ANT-resilient (ANT-Res; n = 8) based on whether, compared to baseline, the rats showed a decrease or no change/increase in REM during the first 4 h following ST. Post-ST ANT microinjected into BLA attenuated the fear-conditioned reduction in REM in ANT-Vul rats on CTX1, but did not significantly alter REM in ANT-Res rats. However, compared to Veh treated rats, REM was reduced in ANT treated rats on CTX2. There were no group differences in freezing or SIH across conditions. Therefore, CRFR1 in BLA plays a role in mediating individual differences in sleep responses to stress and in the extinction of fear conditioned changes in sleep.

Keywords: Basolateral amygdala; Corticotropin releasing factor; Fear conditioning; Rapid eye movement sleep; Resilience; Vulnerability.

Publication types

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

MeSH terms

  • Adaptation, Psychological / drug effects*
  • Animals
  • Basolateral Nuclear Complex / drug effects*
  • Basolateral Nuclear Complex / metabolism
  • Body Temperature / drug effects*
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Electroencephalography
  • Fear / drug effects*
  • Fear / psychology
  • Freezing Reaction, Cataleptic / drug effects*
  • Male
  • Memory / drug effects
  • Physical Conditioning, Animal / physiology
  • Physical Conditioning, Animal / psychology
  • Pyrimidines / pharmacology*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Wistar
  • Sleep / drug effects*
  • Sleep / physiology
  • Sleep, REM / drug effects


  • Pyrimidines
  • Pyrroles
  • antalarmin
  • Corticotropin-Releasing Hormone