Stress and central Urocortin increase anxiety-like behavior in the social interaction test via the CRF1 receptor

Eur J Pharmacol. 2005 Feb 21;509(2-3):145-53. doi: 10.1016/j.ejphar.2004.12.030.

Abstract

Corticotropin releasing factor (CRF) and Urocortin are important neurotransmitters in the regulation of physiological and behavioral responses to stress. Centrally administered CRF or Urocortin produces anxiety-like responses in numerous animal models of anxiety disorders. Previous studies in our lab have shown that Urocortin infused into the basolateral nucleus of the amygdala produces anxiety-like responses in the social interaction test. Subsequently, in the current study we prepared a specific CRF1 receptor antagonist (N-Cyclopropylmethyl-2,5-dimethyl-N-propyl-N'-(2,4,6-trichloro-phenyl)-pyrimidine-4,6-diamine, NBI3b1996) to examine in this paradigm. This CRF1 receptor antagonist inhibited the ex vivo binding of 125I-sauvagine to rat cerebellum with an ED50 of 6 mg/kg, i.p. NBI3b1996 produced a dose-dependent antagonism of Urocortin-induced anxiety-like behavior in Social Interaction test with an ED50 of 6 mg/kg, i.p. The compound had no effect on baseline social interaction. In addition, the CRF1 receptor antagonist prevented the stress-induced decrease in social interaction. These results provide further support for the CRF1 receptor in anxiety-like behavior and suggest this pathway is quiescent in unstressed animals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphibian Proteins
  • Animals
  • Anxiety Disorders / etiology
  • Anxiety Disorders / physiopathology*
  • Autoradiography
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / pharmacology*
  • Dose-Response Relationship, Drug
  • Iodine Radioisotopes
  • Male
  • Peptide Hormones
  • Peptides / metabolism
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Restraint, Physical
  • Social Behavior*
  • Stress, Psychological / physiopathology*
  • Urocortins

Substances

  • Amphibian Proteins
  • Iodine Radioisotopes
  • N-cyclopropylmethyl-2,5-dimethyl-N-propyl-N'-(2,4,6-trichloro-phenyl)-pyrimidine-4,6-diamine
  • Peptide Hormones
  • Peptides
  • Pyrimidines
  • Receptors, Corticotropin-Releasing Hormone
  • Urocortins
  • CRF receptor type 1
  • sauvagine
  • Corticotropin-Releasing Hormone