Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats.
Tumor necrosis factor-alpha (TNFalpha) was infused into the subarachnoid space of the rat rostral basal forebrain, which was previously defined as a prostaglandin (PG) D2-sensitive, sleep-promoting zone. TNFalpha increased the amount of slow-wave sleep (SWS), decreased that of paradoxical sleep (PS), and caused fever and anorexia. The TNFalpha-induced SWS enhancement, fever and anorexia were all blocked by co-infusion of diclofenac, a non-selective cyclooxygenase (COX) inhibitor, and by pretreatment with NS-398, a COX-2-specific inhibitor. In striking contrast, the TNFalpha-induced suppression of PS was not affected by the inhibitors. These results indicate that COX-2-mediated hyperproduction of PGs is critically involved in the enhancement of SWS, fever, and anorexia but not in the suppression of PS, caused by TNFalpha infused into the PGD2-sensitive zone.
Terao
A
A
Department of Molecular Behavioural Biology, Osaka Bioscience Institute, Suita City, Japan.
Matsumura
H
H
Yoneda
H
H
Saito
M
M
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D016548:Prosencephalon / Q000187:drug effects; D015230:Prostaglandin D2 / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004008:Diclofenac; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2