Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 77, Issue 3, Pages 447-455Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2003.12.010
Keywords
anxiety; amygdala; stress; social interaction; corticosterone; c-fos
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Studies suggest that behavioral, genomic, and endocrine functions mediated by central corticotropin-releasing factor (CRF)-containing circuits may be differentially regulated. However, this hypothesis has never been tested directly by simultaneous assessment of distinct CRF-mediated responses within the same animal. The present study addressed this issue by concurrently examining the effects of central CRF infusions on anxiety responses, plasma corticosterone release, and c-fos mRNA induction within limbic brain circuits. Bilateral intracerebroventricular (icv) infusions of CRF (0.1 - 10 mug total) dose-dependently reduced exploratory behavior in a novel open field, increased circulating corticosterone (CORT) levels and augmented c-fos mRNA expression in the central nucleus of the amygdala (CeA) and the hypothalamic paraventricular nucleus (PVN). Plasma CORT levels increased significantly after 0.1 mug CRF, whereas behavioral and genomic responses required at least 1 mug CRF, suggesting that the distinct responses mediated by CRF are differentially regulated. Further characterization of intracerebroventricular CRF at 1 mug also demonstrated a disruption of social interaction behavior. The majority of behavioral effects and the elevated c-fos mRNA expression were attenuated by 10 mg/kg DMP696, a CRF1 antagonist. However, plasma CORT elevation required 30 mg/kg DMP696 for attenuation. Thus, our studies demonstrate a greater sensitivity of the hypothalamic-pituitary-adrenal axis to intracerebroventricular CRF compared with the induction of innate fear-like responses and associated genomic changes. (C) 2004 Published by Elsevier Inc.
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