Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses

Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1291-308. doi: 10.1016/j.pnpbp.2009.06.022. Epub 2009 Jul 10.


The medial division of the central nucleus of the amygdala (CeA(M)) and the lateral division of the bed nucleus of the stria terminalis (BNST(L)) are closely related. Both receive projections from the basolateral amygdala (BLA) and both project to brain areas that mediate fear-influenced behaviors. In contrast to CeA(M) however, initial attempts to implicate the BNST in conditioned fear responses were largely unsuccessful. More recent studies have shown that the BNST does participate in some types of anxiety and stress responses. Here, we review evidence suggesting that the CeA(M) and BNST(L) are functionally complementary, with CeA(M) mediating short- but not long-duration threat responses (i.e., phasic fear) and BNST(L) mediating long- but not short-duration responses (sustained fear or 'anxiety'). We also review findings implicating the stress-related peptide corticotropin-releasing factor (CRF) in sustained but not phasic threat responses, and attempt to integrate these findings into a neural circuit model which accounts for these and related observations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Anxiety / metabolism
  • Anxiety / pathology*
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fear*
  • Light
  • Methylcellulose / analogs & derivatives
  • Methylcellulose / pharmacology
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism*
  • Stress, Psychological


  • GSK876008
  • Methylcellulose
  • Corticotropin-Releasing Hormone