Effect of a chronic stress on CRF neuronal activity and expression of its type 1 receptor in the rat brain

The purpose of this study was to compare the effect of an acute versus a chronic immobilization stress on the genetic expression of c-fos and corticotropin-releasing factor type 1 receptor (CRF1 receptor) in the paraventricular nucleus (PVN) of the rat hypothalamus. Male Sprague-Dawley rats were exposed to either a single 90-min immobilization stress or the same session for 11 consecutive days. Animals were deeply anesthetized before (control); immediately, 1.5, 3, 6, or 12 h after the acute stress; or after the last session of the repeated exposures to immobilization. Coronal frozen sections (30 mu m) of the brains were cut and mRNAs encoding the rat c-ibs and CRF1 receptor were assayed by in situ hybridization histochemistry using S-35-labeled riboprobes. Localization of these transcripts within PVN CRF-immunoreactive (ir) neurons was also determined. The expression of the mRNA encoding either c-fos or CRF1 receptor was barely detectable to low in the PVN of control animals, but the acute stress session induced a robust signal for both transcripts in this endocrine nucleus. Numerous CRF-ir neurons were positive for the gene encoding either c-fos or CRF1 receptor in the PVN of acutely stressed animals. In contrast, the PVN of chronically stressed animals displayed a significantly lower CRF1 receptor mRNA signal after the last stress session. In these animals, stress-induced transcription of c-fos mRNA occurred in the magnocellular PVN 90 min after the end of the last stress session but only a low signal was detected in the parvocellular division. Moreover, very few CRF-ir neurons of the PVN expressed either the CRF1 receptor or c-fos transcript in chronically stressed rats. These data provide evidence for an adaptive cellular mechanism involving an attenuated action of CRF within the PVN in response to repeated homotypic stress exposures.