l-Serine induces sedative and hypnotic effects acting at GABA A receptors in neonatal chicks

• Published in: European journal of pharmacology 2008-12, Vol.599 (1), p.86-90
• Main Authors: Shigemi, Kazutaka, Tsuneyoshi, Yousuke, Hamasu, Kousuke, Han, Li, Hayamizu, Kohsuke, Denbow, D. Michael, Furuse, Mitsuhiro
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Animals, Newborn; Chick; Chickens; Disease Models, Animal; GABA A receptor; Glycine - pharmacology; Glycine receptor; Hypnotics and Sedatives - pharmacology; L-Serine; Male; Picrotoxin; Picrotoxin - pharmacology; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Receptors, Glycine - drug effects; Receptors, Glycine - metabolism; Serine - pharmacology; Stress, Psychological - metabolism; Strychnine
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.09.036

Intracerebroventricular injection of l-serine has been shown to have sedative and hypnotic effects on neonatal chicks exposed to acute stressful conditions. However, the mechanism by which l-serine induces these effects is unclear. The present study was conducted to clarify the mechanism by l-serine. The involvement of γ-aminobutyric acid (GABA) A receptors on the effect of l-serine was investigated using the GABA A receptor antagonist picrotoxin. Co-administration of picrotoxin attenuated the sedative and hypnotic effect of l-serine. Further, we also investigated the involvement of glycine receptors since l-serine is suggested to act as the α-homomeric glycine receptor agonist. Glycine similarly induced sedative and hypnotic effects in chicks, but its effect was attenuated by the glycine receptor antagonist strychnine. Therefore, whether the effect of l-serine was mediated through the glycine receptor was investigated using l-serine and strychnine. The effect of l-serine was inhibited by picrotoxin, but not strychnine. It appears that l-serine induces sedative and hypnotic effects by enhancing inhibitory neurotransmission via GABA A receptors.