Interleukin-1β induces sleep independent of prostaglandin D2in rats and mice.
Interleukin-1β (IL-1β) and prostaglandin (PG) D2are endogenous sleep-promoting substances. Since it was reported that a highly selective cyclooxygenase-2 (COX-2) inhibitor, NS398, completely inhibited IL-1β-induced sleep in rats, IL-1β-induced sleep had been believed to be mediated by prostanoids, most probably PGD2. However, in the present study, pretreatment of rats with NS398 (3mg/kg) did not suppress the 64.2% increased non-rapid eye movement (non-REM, NREM) sleep during infusion of IL-1β (10ng) for 6h in the nocturnal (active) period between 23:00 and 5:00 into the subarachnoid space of the PGD2-sensitive sleep-promoting zone of the basal forebrain. Meanwhile, IL-1β at doses of 1.7 and 5μg/kg also significantly increased NREM sleep for 6h after intraperitoneal injection at 20:00 (light-off time) by 76.8% and 121.1%, respectively, in wild-type (WT) mice, by 67.7% and 147.3%, respectively, in WT mice pretreated with NS398 (5mg/kg) and by 108.9% and 121.6%, respectively, in PGD2receptor (DP1R) knockout mice. These results indicate that IL-1β-induced NREM sleep is independent of the PGD2/DP1R system and other COX-2-derived prostaglandins in rats and mice.
State Key Laboratory of Medical Neurobiology, Department of Pharmacology, Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: 071101009@fudan.edu.cn.
Bin-Jia
BJ
Zhang
State Key Laboratory of Medical Neurobiology, Department of Pharmacology, Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: shaoshurong1988@163.com.
Shu-Rong
SR
Shao
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan. Electronic address: aritake.kosuke.gt@u.tsukuba.ac.jp.
Kosuke
K
Aritake
Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan. Electronic address: takeuchi@kobepharma-u.ac.jp.
Atsuko
A
Takeuchi
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan. Electronic address: urade.yoshihiro.ft@u.tsukuba.ac.jp.
Yoshihiro
Y
Urade
State Key Laboratory of Medical Neurobiology, Department of Pharmacology, Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: huangzl@fudan.edu.cn.
Zhi-Li
ZL
Huang
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan. Electronic address: lazarus.michael.ka@u.tsukuba.ac.jp.
Michael
M
Lazarus
State Key Laboratory of Medical Neurobiology, Department of Pharmacology, Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: quweimin@fudan.edu.cn.
Wei-Min
WM
Qu
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009578:Nitrobenzenes / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D015230:Prostaglandin D2 / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D006993:Hypnotics and Sedatives; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D009578:Nitrobenzenes; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D011994:Recombinant Proteins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor
COX-2 inhibition; body temperature; cytokine; prostaglandin D(2); sleep; slow-wave activity