Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase.
Prostaglandin (PG) D2 has been postulated to be an endogenous sleep-promoting factor in rats, and SeCl4 and Na2SeO3 recently have been shown to inhibit the PGD synthase (prostaglandin-H2 D-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 microliter per min and higher, and the inhibition was almost complete at rates greater than 200 pmol/0.2 microliter per min. The effect was reversible and was followed by a rebound. Na2SeO3 exhibited similar effects, but Na2SO3 did 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 SeCl4 as 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.
Osaka Bioscience Institute, Japan.
H
H
Matsumura
R
R
Takahata
O
O
Hayaishi
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular / Q000295:instrumentation / Q000379:methods; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000037:antagonists & inhibitors*; D054834:Lipocalins; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D064586:Selenic Acid; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D018036:Selenium Compounds; D012890:Sleep / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002712:Chlorides; D054834:Lipocalins; D018036:Selenium Compounds; C070974:selenium tetrachloride; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D012643:Selenium; D064586:Selenic Acid; D004229:Dithiothreitol