Suppression of sleep by prostaglandin synthesis inhibitors in unrestrained rats.
Sleep-suppressive activity of prostaglandin synthesis inhibitors, diclofenac sodium (DF) and indomethacin (IM), was examined in unrestrained male rats. An intraperitoneal injection of 5 mg/kg IM, or an oral administration of 5 mg/kg DF and 10 mg/kg IM at an early phase of the light period transiently decreased slow wave sleep (SWS) and paradoxical sleep (PS) to 30-62% and 0-38%, respectively, of the control level in the first hour. An intravenous infusion of 0.4 mg DF or 0.4 mg IM or an intracerebroventricular infusion of 0.04 mg DF continuously during a 10-h diurnal period resulted in a significant decrease in SWS and PS by 9-17% and 17-21%, respectively, from the baseline value in the 12-h light period. The DF infusion was accompanied by a rebound rise in the nocturnal SWS and PS and the subsequent diurnal PS. The results indicate that the depletion of prostaglandin(s) in the brain is responsible for the DF- and IM-induced suppression of sleep.
Naito
K
K
Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Japan.
Osama
H
H
Ueno
R
R
Hayaishi
O
O
Honda
K
K
Inoué
S
S
D000284:Administration, Oral; D000818:Animals; D004008:Diclofenac / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects*
D011453:Prostaglandins; D004008:Diclofenac; D007213:Indomethacin