COMPARATIVE, BEHAVIORAL AND ELECTROCORTICAL EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1 MICROINJECTED INTO THE LOCUS-COERULEUSOF RAT

The behavioural and electrocortical (ECoG) effects of human recombinan t tumor necrosis factor-alpha (hrTNF-alpha) and various forms of inter leukin-1 (IL-1) microinjected into the locus coeruleus (LC) of rats we re studied. IL-1 induced a typical, dose-dependent, behavioural sedati on and/or sleep which was associated with ECoG synchronization. IL-1 b eta appeared more potent than IL-1 alpha. During sleep induced by the various forms of IL-1 a dose-dependent increase in total voltage power (0.25-16 Hz) as well as in the 3-6, 6-9 and sometimes 0.25-3 Hz frequ ency bands was observed. The behavioural and ECoG effects of IL-1 beta were blocked in rats pretreated with anti-IL-1 monoclonal antibodies. The microinjection of hrTNF-alpha into the LC produced a typical patt ern characterized by a first short lasting (20-30 ; min) phase of beha vioural arousal and ECoG desynchronization, followed by a longer lasti ng (45-80 min) phase of behavioural sedation and/or sleep and ECoG syn chronization characterized by an increase in total voltage power as we ll as in the 3-6, 6-9 and sometimes 0.25-3 Hz frequency bands. The beh avioural and ECoG effects of hrTNF-alpha were antagonized by a pretrea tment (15 min before) with specific anti-TNF-alpha polyclonal antibodi es. In addition, a pretreatment with anti-IL-1 receptor monoclonal ant ibodies was unable to significantly affect the stimulation of behaviou r and ECoG desynchronization effects elicited by hrTNF-alpha whilst th e same pretreatment completely prevent the sedative and ECoG synchroni zing phase elicited by the microinjection of hrTNF-alpha into the LC. These results are consisted with the hypothesis that the sedative and/ or soporific behavioural and ECoG changes of hrTNF-alpha are mediated, at LC level, through a local IL-1 release.