Intravenous administration of inorganic selenium compounds, inhibitors of prostaglandin D synthase, inhibits sleep in freely moving rats.
Prostaglandin (PG) D2 has been postulated to be an endogenous sleep-promoting factor. Biosynthesis of PGD2 is catalyzed by PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2), the activity of which is inhibited by inorganic selenium compounds such as SeCl4 and Na2SeO3. 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 systemically, 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. SeCl4 time- and dose-dependently inhibited sleep at infusion rates of 5, 7.5, 10 and 20 nmol/microliters per min. During the SeCl4 infusion at 20 nmol/microliters per min, slow-wave sleep and paradoxical sleep were reduced to 63% and 50% of their respective baseline values. Na2SeO3 exhibited a similar sleep inhibition, though Na2SO3 was ineffective. Infusion of SeCl4 at 10 nmol/microliters 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 SeCl4 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.
Takahata
R
R
Department of Neuropsychiatry, Osaka Medical College, Japan.
Matsumura
H
H
Kantha
S S
SS
Kubo
E
E
Kawase
K
K
Sakai
T
T
Hayaishi
O
O
D000818:Animals; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D007262:Infusions, Intravenous; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000037:antagonists & inhibitors*; D054834:Lipocalins; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018036:Selenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D018038:Sodium Selenite / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
D002712:Chlorides; D054834:Lipocalins; D018036:Selenium Compounds; C070974:selenium tetrachloride; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D018038:Sodium Selenite