Intracerebroventricular injection of glutathione and its derivative induces sedative and hypnotic effects under an acute stress in neonatal chicks

Glutathione-related enzymes glyoxalase 1 and glutathione reductase 1 regulates anxiety in mice. To clarify the central function of glutathione as a neurotransmitter in the stress reaction, the effect of intracerebroventricular (i.c.v.) injection of reduced (GSH) (0.5, 1, 2 μmol) and oxidized (GSSG) glutathione (0.25, 0.5, 1 μmol) were investigated under an isolation-induced stress in the neonatal chick. Both GSH and GSSG dose-dependently decreased distress vocalizations and induced sleep-like behavior in chicks under acute stressful conditions. However, which glutathione is actually responsible for inducing sleep was unclear since glutathione cycles between GSH and GSSG in which two tripeptides are linked by a disulfide bond. Therefore, the behavior of chicks was monitored following the i.c.v. injection of S-methylglutathione (SMG) (0.0625, 0.25, 1 μmol). SMG does not form a disulfide bond due to the methylation of the SH group of the cysteine moiety. SMG had similar effects as observed in GSH and GSSG. In conclusion, glutathione and its derivative have sedative and hypnotic effects, and might be effective in improving psychic stress such as anxiety.