Oxidized glutathione promotes sleep in rabbits

Glutatione is implicated in sleep regulation. There are circadian changes in brain glutathione levels, and nocturnal intracerebroventricular (i.c.v.) slow infusion of oxidized glutathione (GSSG) or reduced glutathione (GSH) promotes rapid-eye-movement sleep (REMS) and non-REMS (NREMS) in rats. In the present experiments, we tested the effects of GSSG on duration of sleep, NREMS intensity, and brain temperature in another species, rabbits. Male New Zealand rabbits were injected with isotonic NaCl on a baseline day and one dose of GSSG on the test day [0.15, 1.5, 15, and 150 microg/rabbit, i.c.v., or 1.5 or 15 mg/kg intravenously (i.v.)]. Electroencephalogram (EEG), motor activity, and brain temperature were recorded for 6 h. Injection of 15 microg GSSG i.c.v. significantly increased the time spent in NREMS in the first 3 h after the injection. Injection of 0.15, 1.5, and 150 microg i.s.v. GSSG, as well as systemic injections of GSSG did not affect NREMS. Intensity of NREMS as measured by EEG slow-wave activity during NREMS, and brain temperature were not affected by any of the treatments. These results are consistent with the hypothesis that glutathione may be a sleep-inducing factor in the brain.