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The Journal of Neuroscience, August 15, 1998, 18(16):6599-6607

Interleukin-1 Induces Slow-Wave Sleep at the Prostaglandin D₂-Sensitive Sleep-Promoting Zone in the Rat Brain

Akira Terao^{1, 2}, Hitoshi Matsumura^{1, 3}, and Masayuki Saito²

¹ Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita City, Osaka 565-0874, Japan, ² Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan, and ³ Department of Neuropsychiatry, Osaka Medical College, Takatsuki City, Osaka 569-8686, Japan

To determine the site of action of the sleep-promoting effect of interleukin-1 (IL-1), we continuously infused (between 11 P.M. and 5 A.M.) murine recombinant IL-1 into seven different locations in the ventricular and subarachnoid systems of the brain in freely moving rats. When IL-1 was infused at 10 ng/6 hr into the subarachnoid space underlying the ventral surface of the rostral basal forebrain, which previously was defined as the "prostaglandin (PG) D₂-sensitive sleep-promoting zone" (PGD₂-SZ), the total amount of slow-wave sleep (SWS) increased by 110.7 min (IL-1 was 208.1 ± 14.3 min vs control at 97.4 ± 9.3 min; n = 8; p < 0.01 by paired Student's t test) from the baseline control level obtained under continuous infusion of saline vehicle. The hourly SWS during the infusion period reached the level of daytime SWS, the physiological maximum, whereas paradoxical sleep (PS) was decreased transiently. This site of action for the SWS promotion was dissociated from the site in the third ventricle sensitive to the IL-1-mediated PS suppression, fever, and anorexia. The SWS increase caused by IL-1 infusion into the PGD₂-SZ was blocked completely by coadministered diclofenac, a nonselective cyclooxygenase (COX) inhibitor. Pretreatment of rats with NS-398 or piroxicam (3 mg/kg of body weight, i.p.), which are said, respectively, to possess high and relative specificity for the COX-2 enzyme, also blocked the SWS-promoting effect of IL-1. We present a hypothesis that IL-1 induces SWS, at least in part, via COX-2-mediated PG production in the PGD₂-SZ.

Key words: interleukin-1; prostaglandin D₂; slow-wave sleep; subarachnoid space; ventral surface of the rostral basal forebrain; COX-2

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18166599-09$05.00/0

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