Corticotropin releasing factor type-1 receptor antagonism in the dorsolateral bed nucleus of the stria terminalis disrupts contextually conditioned fear, but not unconditioned fear to a predator odor

Psychoneuroendocrinology. 2016 Aug:70:17-24. doi: 10.1016/j.psyneuen.2016.04.021. Epub 2016 Apr 28.


The bed nucleus of the stria terminalis (BNST) plays a critical role in fear and anxiety. The BNST is important for contextual fear learning, but the mechanisms regulating this function remain unclear. One candidate mechanism is corticotropin-releasing-factor (CRF) acting at CRF type 1 receptors (CRFr1s). Yet, there has been little progress in elucidating if CRFr1s in the BNST are involved in different types of fear (conditioned and/or unconditioned). Therefore, the present study investigated the effect of antalarmin, a potent CRFr1 receptor antagonist, injected intracerebroventricularly (ICV) and into the dorsolateral BNST (LBNST) during single trial contextual fear conditioning or exposure to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). Neither ICV nor LBNST antalarmin disrupted unconditioned freezing to TMT. In contrast, ICV and LBNST antalarmin disrupted the retention of contextual fear when tested 24h later. Neither ICV nor LBNST antalarmin affected baseline or post-shock freezing-indicating antalarmin does not interfere with the early phases of contextual fear acquisition. Antalarmin did not (1) permanently affect the ability to learn and express contextual fear, (2) change responsivity to footshocks, or (3) affect the ability to freeze. Our findings highlight an important role for CRFr1s within the LBNST during contextually conditioned fear, but not unconditioned predator odor fear.

Keywords: Bed nucleus of the stria terminalis; Context fear; Corticotropin releasing factor; Fear conditioning; Predator odor; TMT.

MeSH terms

  • Animals
  • Behavior, Animal
  • Conditioning, Classical
  • Corticotropin-Releasing Hormone / metabolism
  • Emotions
  • Fear / physiology*
  • Male
  • Odorants
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism*
  • Thiazoles / pharmacology


  • 2,5-dihydro-2,4,5-trimethylthiazoline
  • Pyrimidines
  • Pyrroles
  • Receptors, Corticotropin-Releasing Hormone
  • Thiazoles
  • antalarmin
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone