EFFECT OF A CHRONIC STRESS ON CRF NEURONAL-ACTIVITY AND EXPRESSION OFITS 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 an d corticotropin-releasing factor type 1 receptor (CRF1 receptor) in th e paraventricular nucleus (PVN) of the rat hypothalamus. Male Sprague- Dawley rats were exposed to either a single 90-min immobilization stre ss or the same session for 11 consecutive days. Animals were deeply an esthetized 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 c ut and mRNAs encoding the rat c-ibs and CRF1 receptor were assayed by in situ hybridization histochemistry using S-35-labeled riboprobes. Lo calization of these transcripts within PVN CRF-immunoreactive (ir) neu rons was also determined. The expression of the mRNA encoding either c -fos or CRF1 receptor was barely detectable to low in the PVN of contr ol animals, but the acute stress session induced a robust signal for b oth transcripts in this endocrine nucleus. Numerous CRF-ir neurons wer e positive for the gene encoding either c-fos or CRF1 receptor in the PVN of acutely stressed animals. In contrast, the PVN of chronically s tressed animals displayed a significantly lower CRF1 receptor mRNA sig nal after the last stress session. In these animals, stress-induced tr anscription of c-fos mRNA occurred in the magnocellular PVN 90 min aft er the end of the last stress session but only a low signal was detect ed in the parvocellular division. Moreover, very few CRF-ir neurons of the PVN expressed either the CRF1 receptor or c-fos transcript in chr onically stressed rats. These data provide evidence for an adaptive ce llular mechanism involving an attenuated action of CRF within the PVN in response to repeated homotypic stress exposures.