THE ROLE OF CEREBRAL NORADRENERGIC SYSTEMS IN THE FOS RESPONSE TO INTERLEUKIN-1

Peripheral administration of interleukin-1 (IL-1) has been shown to ac tivate induction of Fos in the brain, but the mechanism is not known. Because cerebral noradrenergic systems have been implicated in Fos ind uction, we studied the IL-1-induced appearance of Fos in mice pretreat ed with 6-hydroxydopamine (6-OHDA) which depleted cerebral norepinephr ine (NE) by more than 90%, but did not significantly alter dopamine. I ntraperitoneally injected IL-1 beta increased Fos in several brain reg ions, but most obviously in the hypothalamic paraventricular nucleus ( PVN). Pretreatment with 6-OHDA substantially reduced the IL-1-induced Fos increase in the PVN which was no longer statistically significant. When the 6-OHDA treatment was preceded by administration of desmethyl imipramine which prevents NE depletion, IL-1 treatment increased Fos i n the PVN, suggesting that the effect of 6-OHDA was indeed related to the depletion of NE. These results suggest that the noradrenergic inne rvation of the PVN is involved in the IL-1-induced induction of Fos in the PVN. By contrast with previous experiments in rats, the IL-1-indu ced increase in plasma corticosterone was not significantly altered by the 6-OHDA pretreatment in mice.