Reduced glutathione regulates sleep in unrestrained rats by producing oxidized glutathione

The present study was conducted to examine whether reduced glutathione (GSH), a naturally occurring tripeptide in the brain, exerts somnogenic activity in freely behaving rats, since its dimer oxidized glutathione (GSSG) is a potent endogenous sleep-promoting substance. Nocturnal 10-h intracerebroventricular (icv) infusion of 50 nmol GSH increased amount of non-rapid-eye-movement (nonREM) sleep during the 12-h dark period (maximally 21 % above the baseline). Dose-response relations exhibited a bell shape at 4 different doses in a range 10-100 nmol. However, inhibition of GSH biosynthesis by diurnal 10-h icv infusion of a GSH peroxidase inhibitor, N-ethylmaleimide (NEM), at 4 different doses in a range 0.01-10 μmol, dose-dependently brought about suppression of both nonREM and REM sleep. These results indicate that GSSG biosynthesized from GSH is actually responsible for the GSH-induced enhancement of sleep.