Corticotropin-releasing factor (CRF) plays a role in coordinating endocrine, physiological and behavioral responses to stressful stimuli. We have previously reported that centrally administered CRF rapidly induces c-fos mRNA expression in most areas that express c-fos following stress: the limbic structures including the hippocampus, amygdala, septal nucleus and hypothalamic nuclei such as the paraventricular nucleus (PVN), and brainstem nuclei such as Barrington's nucleus and locus ceruleus (LC). These results suggest several candidate structures through which CRF could exert its effects on the central nervous system. The aim of the present study was to explore the role of endogenous CRF in activating these brain regions after stress using a specific CRF receptor antagonist, alpha-helical CRF(9-41). One hundred micrograms of alpha-helical CRF or vehicle alone was injected into the right lateral ventricle of rats. Thirty minutes later, they were exposed to restraint stress for 30 min, and the rat brain was then perfused transcardially with 4% paraformaldehyde. Another control group of rats was sacrificed 60 min after intracerebroventricular (ICV) injection of vehicle without restraint. In situ hybridization was performed by hybridizing sections with 35S-labeled c-fos cRNA probes. ICV injection of vehicle alone induced a weak c-fos mRNA expression in the lateral septal nucleus (LSV) and PVN in the rats without restraint, probably due to the mild stress of ICV injection. Restraint stress produced strong c-fos mRNA induction in the PVN, LSV, LC and Barrington's nucleus. However, ICV injection of 100 micrograms alpha-helical CRF significantly decreased c-fos mRNA expression in the PVN without affecting c-fos mRNA induction in the LSV, LC, or Barrington's nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)