Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats

TUMOR necrosis factor-alpha (TNF alpha) was infused into the subarachnoid s pace of the rat rostral basal forebrain, which was previously defined as a prostaglandin (PG) D-2-sensitive, sleep-promoting zone. TNF alpha increased the amount of slow-wave sleep (SWS), decreased that of paradoxical sleep ( PS), and caused fever and anorexia. The TNF alpha-induced SWS enhancement, fever and anorexia were all blocked by co-infusion of diclofenac, a non-sel ective cyclooxygenase (COX) inhibitor, and by pretreatment with NS-398, a C OX-2-specific inhibitor. In striking contrast, the TNF alpha-induced suppre ssion of PS was not affected by the inhibitors. These results indicate that COX-2-mediated hyperproduction of PGs is critically involved in the enhanc ement of SWS, fever, and anorexia but not in the suppression of PS, caused by TNF alpha infused into the PGD(2)-sensitive zone. NeuroReport 9: 3791-37 96 (C) 1998 Lippincott Williams & Wilkins.