Intracerebroventricular administration of corticotropin-releasing factor inducesc-fos mRNA expression in brain regions related to stress responses: comparison with pattern ofc-fos mRNA induction after stress

Abstract

Centrally administered corticotropin-releasing factor (CRF) produces a number of physiological and behavioral changes akin to those elicited by exposure to acute stress. However, the specific brain site of action responsible for the centrally activating property of CRF has not been precisely determined. In this study, we used in situ hybridization histochemistry forc-fos mRNA to map potential neuronal structures activated after intracerebroventricular (i.c.v.) injection of CRF and compared the distribution ofc-fos mRNA with that after stress. Wistar male rats were sacrificed 30, 60, 120 and 180 min after the i.c.v. injection of 1 μg ovine CRF or vehicle alone. Another group of rats was exposed to immobilization stress for 60 min or electrical foot-shock stress (1.5 mA, 1-s duration, 30×) for 15 min and sacrificed before and 30, 60 120 and 180 min after the beginning of stress. Centrally administered CRF rapidly (30–60 min) inducedc-fos mRNA expression in most of the areas that showed hybridization signals forc-fos after stress: the limbic structures, including the piriform cortex, cingulate cortex, the lateral septal nucleus, the hippocampus, the anterior corticomedial and the medial amygdaloid nuclei, the hypothalamic nuclei, such as the paraventricular nucleus, the supraoptic nucleus (SO) and the dorsomedial nucleus (DMD), and some brainstem nuclei like the pontine nucleus, the locus ceruleus (LC) and Barrington's nucleus. The granular layer of the cerebellum, some thalamic nuclei and the habenula also showed by hybridization signals after i.c.v. injection of CRF and stress. However, c-fos induction in the bed nucleus of the stria terminalis, the central nucleus of the amygdala (CeA) and the nucleus tractus solitarius (SOL) was seen only after i.c.v. administration of CRF; in the septohypothalamic nucleus and the superior olive, however, c-fos mRNA expression was observed only after stress. There were no differences in the pattern ofc-fos mRNA expression between the two stress paradigms. In contrast, i.c.v. injection of saline-induced expression ofc-fos mRNA in the piriform cortex, neocortex, cingulate cortex and the amygdala was much less than that seen after i.c.v.-administered CRF as evident in the intensity of the signals. These results suggest that CRF producesc-fos mRNA expression in the brain areas related to stress response, ant that CRF may induce behavioral and neuroendocrine responses through activating these brain structures, such as the limbic system and the hypothalamic nuclei. It is also suggested that the CeA, LC and SOL may be involved in the expression of cardiovascular and autonomic actions as well as an increase in arousal induced by CRF.