Glutatione is implicated in sleep regulation. There are circadian chan
ges in brain glutathione levels, and nocturnal intracerebroventricular
(i.c.v.) slow infusion of oxidized glutathione (GSSG) or reduced glut
athione (GSH) promotes rapid-eye-movement sleep (REMS) and non-REMS (N
REMS) in rats. In the present experiments, we tested the effects of GS
SG on duration of sleep, NREMS intensity, and brain temperature in ano
ther species, rabbits. Male New Zealand rabbits were injected with iso
tonic NaCl on a baseline day and one dose of GSSG on the test day [0.1
5, 1.5, 15, and 150 mu g/rabbit, i.c.v., or 1.5 or 15 mg/kg intravenou
sly (i.v.)]. Electroencephalogram (EEG), motor activity, and brain tem
perature were recorded for 6 h, Injection of 15 mu g GSSG i.c.v. signi
ficantly increased the time spent in NREMS in the first 3 h after the
injection. Injection of 0.15, 1.5, and 150 mu g i.s.v. GSSG, as well a
s systemic injections of GSSG did not affect NREMS. Intensity of NREMS
as measured by EEG slow-wave activity during NREMS, and brain tempera
ture were not affected by any of the treatments. These results are con
sistent with the hypothesis that glutathione may be a sleep-inducing f
actor in the brain. (C) 1998 Elsevier Science Inc.