The effect of CRF and alpha-helical CRF((9-41)) on rat fear responses and amino acids release in the central nucleus of the amygdala

Neuropharmacology. 2009 Aug;57(2):148-56. doi: 10.1016/j.neuropharm.2009.04.016. Epub 2009 May 27.

Abstract

The effects of intracerebroventricular injections of CRF and a non-selective CRF receptor antagonist, alpha-helical CRF((9-41)), on the release of glutamate, aspartate, and GABA in the central nucleus of the amygdala (CeA), were examined in the course of testing rat anxiety-like behaviour in the conditioned fear test (a freezing response), using the microdialysis technique. It was found that CRF (1 microg/rat), given to animals exposed to the stress of novelty only, insignificantly increased the glutamate concentration in the CeA, up to 200% of the control level. In the fear-conditioned animals, the influence of CRF on the local concentration of aspartate, glutamate, and Glu/GABA ratio was much more pronounced (up to a 400% increase above the baseline level of aspartate concentration), preceded an increased expression of anxiety-like responses, and appeared as early as 15 min after the drug administration. The intracerebroventricular administration of alpha-helical CRF((9-41)) (10 microg/rat) significantly decreased the rat freezing responses and increased the local concentration of GABA during the first 30 min of observation. In sum, these are new findings, which show an important role of CRF in the CeA in the regulation of fear-controlled amino acids release and suggest an involvement of amino acids in the central nucleus of the amygdala in the effects of this neurohormone on the expression of conditioned fear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Anxiety / metabolism
  • Aspartic Acid / metabolism
  • Conditioning, Classical
  • Corticotropin-Releasing Hormone / metabolism
  • Corticotropin-Releasing Hormone / pharmacology*
  • Fear / drug effects*
  • Freezing Reaction, Cataleptic
  • Glutamic Acid / metabolism
  • Male
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Wistar
  • Stress, Psychological / metabolism
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amino Acids
  • Peptide Fragments
  • Aspartic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)