Abstract
Astressin, a novel corticotropin releasing factor (CRF) antagonist, has been found to be particularly potent at inhibiting the hypothalamo-pituitary-adrenal axis. The aim of the present study was to determine the effects in rats of astressin in attenuating the anxiogenic-like response produced by social stress and intracerebroventricular (ICV) CRF administration on the elevated plus-maze, and ICV CRF-induced locomotor activation in the rat. Astressin significantly reversed the anxiogenic-like response induced by both social stress and ICV rat/humanCRF (r/hCRF) on the elevated plus-maze, but failed to block the effects of r/hCRF-induced locomotor activity in a familiar environment. When these results were compared to previous studies performed with the same paradigms using other CRF antagonists, astressin showed effects similar to those of D-PheCRF(12-41) on plus-maze performance. However, contrary to α-helicalCRF(9-41) and D-PheCRF(12-41), astressin had no effect on CRF-induced locomotor activity. These results suggest that astressin may have a unique anti-CRF profile compared to previously tested antagonists.
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Acknowledgements
The authors gratefully acknowledge Dr. Frederique Menzaghi for her great advice on the experimental procedures, Robert Lintz, Victoria Risborough, Ilham Polis, and Pete Griffin for their great help and excellent technical assistance, and Mike Arends for his thorough editing. This work was supported by NIH Grant DK 26741 from the National Institute of Diabetes and Digestive and Kidney Diseases. AMB was supported by Grant 1 F05 TW05262-02 from the Fogarty International Center, NIH. The experimental protocols for animals and their care were approved by the Institutional Review Committee for the use of Animal Subjects. This is publication number 11027-NP from The Scripps Research Institute.
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Spina, M., Basso, A., Zorrilla, E. et al. Behavioral Effects of Central Administration of The Novel CRF Antagonist Astressin in Rats. Neuropsychopharmacol 22, 230–239 (2000). https://doi.org/10.1016/S0893-133X(99)00108-6
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DOI: https://doi.org/10.1016/S0893-133X(99)00108-6
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