IL-1-BETA INCREASES NOREPINEPHRINE LEVEL IN RAT FRONTAL-CORTEX - INVOLVEMENT OF PROSTANOIDS, NO, AND GLUTAMATE

The effects of local administration of interleukin-1 beta (IL-1 beta) were studied by using an intracerebral microdialysis technique in rats . A local injection of IL-1 beta (3 and 10 ng) induced an elevation of norepinephrine (NE) concentration in the medial prefrontal cortex (mP FC). IL-1-receptor antagonist (800 ng) completely blocked the IL-1 bet a-induced NE increase. Diclofenac, a cyclooxygenase inhibitor (500 mu M), and N-omega-nitro-Larginine, a nitric oxide (NO) synthase inhibito r (100 mu M), applied through the dialysis probe, did not affect the i nitial rise in NE levels observed 20 min after injection of IL-1 beta but completely suppressed the late phase of IL-1 beta-induced NE incre ase at 40 min and thereafter. In contrast, local perfusion of 6-cyno-7 -nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartic acid (NMDA) glu tamate-receptor antagonist (50 mu M), but not DL-2-amino-5-phosphonova leric acid, an NMDA-receptor antagonist (100 mu M), blocked both phase s of IL-1 beta-induced NE increase. Furthermore, a microinjection of I L-1 beta elevated the extracellular concentration of glutamate in the mPFC. These findings suggest that the IL-1 beta-induced rise in NE lev els in the mPFC is caused by activation of the glutamatergic system an d the glutamate-induced increases in prostanoids and NO.