A cyclooxygenase-2 inhibitor attenuates spontaneous and TNF-alpha-induced non-rapid eye movement sleep in rabbits.
Sleep is regulated in part by the brain cytokine network, including tumor necrosis factor-alpha (TNF-alpha). TNF-alpha activates the transcription factor nuclear factor-kappaB, which in turn promotes transcription of many genes, including cyclooxygenase-2 (COX-2). COX-2 is in the brain and is an enzyme responsible for production of prostaglandin D2. The hypothesis that central COX-2 plays a role in the regulation of spontaneous and TNF-alpha-induced sleep was investigated. Three doses (0.5, 5, and 50 microg) of NS-398, a highly selective COX-2 inhibitor, were injected intracerebroventricularly. The highest dose decreased non-rapid eye movement sleep. The intermediate and highest doses decreased electroencephalographic slow-wave activity; the greatest reduction occurred after 50 microg of NS-398 during the first 3-h postinjection period. Rapid eye movement sleep and brain temperature were not altered by any dose of NS-398. Pretreatment of rabbits with 5 or 50 microg of NS-398 blocked the TNF-alpha-induced increases in non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature. These data suggest that COX-2 is involved in the regulation of spontaneous and TNF-alpha-induced sleep.
Yoshida
Hitoshi
H
Dept. of VCAPP, PO Box 646520, Washington State University, Pullman, WA 99164-6520, USA.
Kubota
Takeshi
T
Krueger
James M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases; D011817:Rabbits; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases