Journal
BRAIN RESEARCH
Volume 952, Issue 2, Pages 188-199Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0006-8993(02)03189-X
Keywords
corticotropin-releasing factor; anxiety; stress; locomotor activity; amphetamine
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Funding
- NIAAA NIH HHS [AA05563] Funding Source: Medline
- NIDDK NIH HHS [DK26741] Funding Source: Medline
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Molecular studies point to a role for the type I 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. (C) 2002 Elsevier Science B.V. All rights reserved.
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