Intravenous administration of inorganic selenium compounds, inhibitors of prostaglandin D synthase, inhibits sleep in freely moving rats

• Published in: Brain research Vol. 623; no. 1; pp. 65 - 71
• Main Authors: Takahata, Ryuichi, Matsumura, Hitoshi, Kantha, Sachi Sri, Kubo, Etsuko, Kawase, Kumiko, Sakai, Toshiaki, Hayaishi, Osamu
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 24.09.1993; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biological and medical sciences; Brain temperature; Catheterization; Chlorides - administration & dosage; Chlorides - pharmacology; Continuous intravenous infusion; Electroencephalogram; Electroencephalography - drug effects; Electromyography - drug effects; Food intake; Fundamental and applied biological sciences. Psychology; Infusions, Intravenous; Intramolecular Oxidoreductases; Isomerases - antagonists & inhibitors; Lipocalins; Male; Rats; Rats, Sprague-Dawley; Selenium Compounds - administration & dosage; Selenium Compounds - pharmacology; Sleep - drug effects; Sleep. Vigilance; Sodium Selenite - administration & dosage; Sodium Selenite - pharmacology; Time Factors; Vertebrates: nervous system and sense organs; Wakefulness - drug effects; Water intake; Continuous intravenous infusion; Water intake; Brain temperature; Electroencephalogram; Catheterization; Food intake; Intravenous administration; Rat; Enzyme; Rodentia; Electrophysiology; Enzyme inhibitor; Electroencephalography; Prostaglandin D2; Prostaglandin synthase; Vertebrata; Mammalia; Sleep; Selenium compound
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(93)90010-K

Prostaglandin (PG) D 2 has been postulated to be an endogenous sleep-promoting factor. Biosynthesis of PGD 2 is catalyzed by PGD synthase (prostaglandin-H 2 d-isomerase, EC 5.3.99.2), the activity of which is inhibited by inorganic selenium compounds such as SeCl 4 and Na 2SeO 3. We recently examined the effect of intracerebroventricular administration of these selenium compounds on sleep in rats, and demonstrated time- and dose-dependent sleep inhibition. To establish whether this effect of selenium is also produced when the compound is administered systematically, we devised a procedure for intravenous catheterization and examined the effect of these selenocompounds on sleep-wake activity in freely moving rats (n = 35). Each test compound was administered into the inferior vena cava continuously between 11.00 and 17.00 h on the experimental day. SeCl 4 time- and dose-dependently inhibited sleep at infusion rates of 5, 7.5, 10 and 20 nmol/ μl per min. During the SeCl 4 infusion at 20 nmol/μl per min, slow-wave sleep and paradoxical sleep were reduced to 63% and 50% of their respective baseline values. Na 2SeO 3 exhibited a similar sleep inhibition, though Na 2SO 3 was ineffective. Infusion of SeCl 4 at 10 nmol/μl per min or below produced no consistent changes in the mean brain temperature, or food and water intake during the infusion period. During the nocturnal period subsequent to SeCl 4 infusion, sleep was increased by a rebound phenomenon, while a decrease in brain temperature and inhibition of food and water intake dose-dependently occurred. We conclude that systemic administration of these PGD synthase inhibitors has a sleep-reducing potency.