Intracerebroventricular injection of l-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks

Four experiments were conducted to clarify the central functions of l-serine and its analogs on an acute stressful condition. Intracerebroventricular (i.c.v.) injection of l-serine (0.21, 0.42 and 0.84 μmol) attenuated stress responses in a dose-dependent fashion, as well as induced sleep, in Experiment 1. The effects of l- and d-serine in Experiment 2, those of l-serine, phosphoserine, acetylserine and l-cysteine in Experiment 3 and those of l-serine, glycine and lysophosphatidylserine in Experiment 4 were compared at an equimolar basis (0.84 μmol). d-Serine, proposed as an endogenous agonist of N-methyl- d-aspatate (NMDA) receptor, did not have sedative and hypnotic effects as observed with l-serine. In contrast, all the analogs and derivatives of l-serine had a sedative effect, although with a different manner in several behavioral markers of stress such as spontaneous activity and distress vocalizations. No significant changes in plasma corticosterone concentration were observed in any experiment. Taken together, the i.c.v. injection of l-serine analogs and its derivatives have sedative and hypnotic effects under an acute stressful condition, which does not involve the hypothalamic–pituitary–adrenal axis. In conclusion, l-serine may be effective in improving anxiety or sleep disorders induced by psychological stressor.