Effects of antalarmin, a CRF type 1 receptor antagonist, on anxiety-like behavior and motor activation in the rat

Brain Res. 2002 Oct 18;952(2):188-99. doi: 10.1016/s0006-8993(02)03189-x.

Abstract

Molecular studies point to a role for the type 1 corticotropin-releasing factor receptor (CRF(1)) in anxiogenic-like and activating effects of CRF and stress. However, CP-154,526, a selective CRF(1) antagonist, has yielded mixed results in such tests. Few studies have examined the behavioral effects of other CRF(1) antagonists. Therefore, we examined the effects of antalarmin, a structurally related analog of CP-154,526, on anxiety-like behavior and motor activation. Antalarmin blocked the anxiogenic-like effect of CRF in the elevated plus maze, without affecting anxiety-like behavior in vehicle-treated animals. Antalarmin decreased spontaneous defensive withdrawal behavior in a novel, brightly illuminated open field. Finally, antalarmin blocked the activating effects of CRF, but not D-amphetamine, without producing motor sedation. These findings indicate that the CRF(1) receptor mediates anxiogenic-like effects of novelty stress and the anxiogenic-like and activating effects of CRF and support the hypothesis that CRF(1) antagonists may be useful for the pharmacotherapy of pathological anxiety.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Corticotropin-Releasing Hormone / pharmacology
  • Corticotropin-Releasing Hormone / physiology
  • Humans
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Receptors, Corticotropin-Releasing Hormone / physiology

Substances

  • Pyrimidines
  • Pyrroles
  • Receptors, Corticotropin-Releasing Hormone
  • antalarmin
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone