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

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.