STRESS AND INTERLEUKIN-1-BETA-INDUCED ACTIVATION OF C-FOS, NGFI-B AND CRF GENE-EXPRESSION THE HYPOTHALAMIC PVN - COMPARISON BETWEEN SPRAGUE-DAWLEY, FISHER-344 AND LEWIS RATS

Various signals are known to activate the hypothalamic-pituitary-adrenal (HPA) axis, an event largely dependent on the release of corticotropin-releasing factor (GRF) which originates mainly from the parvocellular paraventricular nucleus (PVN) of the hypothalamus. These signals include neurogenic stimuli such as exposure to mild electroshocks, and systemic stimuli like administration of cytokines. The HPA axis activity of Lewis rats has been reported to be hyporesponsive to such stimuli, but the exact mechanisms involved in this phenomenon are poorly understood. The present study investigated the effect of footshock exposure and central injection of interleukin ([L)-1 beta, on CRF neuronal activity and gene expression in the PVN of adult male Sprague-Dawley (SD), Fisher-344 (F344j and Lewis (LEW) rats. The animals were deeply anesthetized and rapidly perfused transcardially with a solution of 4% paraformaldehyde 3 h after the beginning of the footshock session (1.5 mA, 2 s duration, L/min over 1 h), or the i.c.v. injection of IL-1 beta (1.00 ng in 10 mu l), mRNA encoding the immediate 'early' genes (IEGs) c-fos and NGFI-B, as well as GRF, were assayed by in situ hybridization histochemistry, while the localization of Fos protein within CRF-immunoreactive (ir) neurons in the PVN was determined using a dual immunostaining protocol. Both stress and IL-1 beta induced robust Fos-ir expression within the parvocellular division of the PVN in all 3 strains. The number of cells immunoreactive for both Fos and CRF proteins in the PVN was similar in SD, F344 and LEW rats following either challenge. While control animals did not display detectable levels of c-fos or NGFI-B mRNA in the PVN, both treatments induced significant expression of these transcripts in this hypothalamic nucleus and no significant differences were observed among SD, F344 and LEW rats. Relative levers of CRF mRNA in the PVN were also significantly and comparably increased following either stress or central IL-1 beta treatment. In contrast, plasma ACTH and corticosterone levels were significantly higher in F344 and SD rats than in LEW animals during the stress session. These results provide further evidence that physical stress and central IL-1 beta can enhance expression of several IEGs, as well as CRF, within the parvocellular division of the PVN. These independent indices of functional activation within parvocellular GRF neurons appear to respond similarly to diverse challenges in adult male SD, F344 and LEW rats. Thus, these findings suggest that the hyporesponsiveness of LEW HPA axis to stress does not seem to be a consequence of a defect in afferent signals to the parvocellular PVN, at least in mature male rats.