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Inhibition of Sleep in Rats by Inorganic Selenium Compounds, Inhibitors of Prostaglandin D Synthase

Prostaglandin (PG) D2has been postulated to be an endogenous sleep-promoting factor in rats, and SeCl4and Na2SeO3recently have been shown to inhibit the PGD synthase (prostaglandin-H2D-isomerase, EC 5.3.99.2) activity of rat brain. The effect of these selenium compounds on sleep-wake activities was...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1991-10, Vol.88 (20), p.9046-9050
Main Authors: Matsumura, Hitoshi, Takahata, Ryuichi, Hayaishi, Osamu
Format: Article
Language:English
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Summary:Prostaglandin (PG) D2has been postulated to be an endogenous sleep-promoting factor in rats, and SeCl4and Na2SeO3recently have been shown to inhibit the PGD synthase (prostaglandin-H2D-isomerase, EC 5.3.99.2) activity of rat brain. The effect of these selenium compounds on sleep-wake activities was examined in freely moving rats along with their effects on brain temperature, food and water intake, and behavior. Test substances were administered for 6 hr into the third ventricle of rats, using a microdialysis technique. SeCl4, time- and dose-dependently, inhibited sleep at perfusion rates of 60 pmol/0.2 μl per min and higher, and the inhibition was almost complete at rates >200 pmol/0.2 μl per min. The effect was reversible and was followed by a rebound. Na2SeO3exhibited similar effects, but Na2SO3did not show any effect on sleep. Simultaneous administration of dithiothreitol eliminated the sleep-inhibiting effects of these selenium compounds. These findings indicate that the decrease in sleep is due to inhibition of the PGD synthase activity in the brain by SeCl4as well as Na2SeO3. During the inhibition of sleep, the rats in general showed an activation of behavior with moderate elevation of brain temperature and a detectable increase in food and water intake, suggesting that the sleep-inhibited state of the rats was similar to the physiological state of wakefulness and that the inhibitory effect was not due to the general toxicity of selenium.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.88.20.9046