OXIDIZED GLUTATHIONE REGULATES PHYSIOLOGICAL SLEEP IN UNRESTRAINED RATS

Oxidized glutathione (GSSG) is an active component of sleep-promoting substance (SPS) which was originally extracted from the brainstems of 24-h sleep-deprived rats. We analyzed somnogenic and thermoregulatory activities of five doses of GSSG in unrestrained rats. A nocturnal 10- h intracerebroventricular infusion of GSSG significantly enhanced slow wave sleep (SWS) at the dosage range from 20 to 50 nmol and paradoxic al sleep (PS) at 25 nmol at the expense of wakefulness during the 12-h dark period. The dose-response relations exhibited a bell shape for b oth SWS and PS. The administration of 25 nmol/10 h GSSG induced the ma ximal increase in the total time of nocturnal sleep (35% above the bas eline for SWS and 86% for PS). The enhancement of sleep was mainly due to an increase in the duration of SWS episodes and in the number of P S episodes. GSSG at 25 nmol/10 h elicited significant fluctuations in brain temperature (T-brain), biphasic hypothermal and hyperthermal rea ctions during the infusion period, followed by a hyperthermal state du ring the subsequent light period of the recovery day and then a hypoth ermal state during the dark period. On the basis of recent literature on the inhibitory action of GSSG on the excitatory synaptic membrane o f rat brain, we speculate that the sleep-enhancing activity of GSSG wa s caused by its physiological modulation on the glutamatergic neurotra nsmission in the brain.