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.
Zorrilla
Eric P
EP
Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. ezorrilla@scripps.edu
Valdez
Glenn R
GR
Nozulak
Joachim
J
Koob
George F
GF
Markou
Athina
A
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D000099052:CRF Receptor, Type 1
D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone