Anxiogenic effects of CGRP within the BNST may be mediated by CRF acting at BNST CRFR1 receptors

Behav Brain Res. 2013 Apr 15;243:286-93. doi: 10.1016/j.bbr.2013.01.024. Epub 2013 Feb 1.


Calcitonin gene-related peptide (CGRP) acting within the bed nucleus of the stria terminalis (BNST) increases anxiety as well as neural activation in anxiety-related structures, and mediates behavioral stress responses. Similar effects have been described following intra-ventricular as well as intra-BNST infusions of the stress-responsive neuropeptide, corticotropin releasing factor (CRF). Interestingly, CGRP-positive terminals within the lateral division of the BNST form perisomatic baskets around neurons that express CRF, suggesting that BNST CGRP could exert its anxiogenic effects by increasing release of CRF from these neurons. With this in mind, the present set of experiments was designed to examine the role of CRFR1 signaling in the anxiogenic effects of CGRP within the BNST and to determine whether CRF from BNST neurons contributes to these effects. Consistent with previous studies, we found that 400 ng CGRP infused bilaterally into the BNST increased the acoustic startle response and induced anxiety-like behavior in the elevated plus maze compared to vehicle. Both of these effects were attenuated by 10mg/kg PO of the CRFR1 antagonist, GSK876008. GSK876008 alone did not affect startle. An intra-BNST infusion of the CRFR1 antagonist CP376395 (2 μg) also blocked increases in acoustic startle induced by intra-BNST infusion of CGRP, as did virally-mediated siRNA knockdown of CRF expression locally within the BNST. Together, these results suggest that the anxiogenic effects of intra-BNST CGRP may be mediated by CRF from BNST neurons acting at local CRFR1 receptors.

Publication types

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

MeSH terms

  • Aminopyridines / administration & dosage
  • Aminopyridines / pharmacology*
  • Animals
  • Calcitonin Gene-Related Peptide / administration & dosage
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / physiology*
  • Catheterization / methods
  • Cells, Cultured
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / physiology*
  • Genetic Vectors / genetics
  • Male
  • Maze Learning / drug effects
  • Methylcellulose / administration & dosage
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / pharmacology
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / physiology*
  • Reflex, Startle / drug effects*
  • Reflex, Startle / genetics
  • Septal Nuclei / drug effects*
  • Septal Nuclei / pathology


  • (3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine
  • Aminopyridines
  • GSK876008
  • RNA, Small Interfering
  • Receptors, Corticotropin-Releasing Hormone
  • Methylcellulose
  • Corticotropin-Releasing Hormone
  • Calcitonin Gene-Related Peptide