Orally administered l-ornithine reduces restraint stress-induced activation of the hypothalamic-pituitary-adrenal axis in mice

► Orally administered l-ornithine significantly decreased corticosterone levels. ► Endogenous monoamine release was investigated using in vivo microdialysis. ► 5-HIAA, DOPAC and HVA were not significantly changed immediately. ► Changes of corticosterone were not related to brain monoamine metabolisms. In a previous study, we confirmed that orally administered l-ornithine can be transported into the brain of mice. In addition, orally administered l-ornithine, within a limited dose range, had an anxiolytic-like effect in the elevated plus-maze test. However, the mechanism by which orally administered l-ornithine reduced the stress response in mice is still unclear. Experiment 1 determined whether orally administered l-ornithine could reduce the stress-induced activation of hypothalamic-pituitary-adrenal axis. Mice were orally administered l-ornithine (0, 0.75, 1.5 and 3mmol/10ml/kg, p.o.), and restrained for 30min from 30min post administration. There was a significant decrease in the corticosterone levels in the group receiving 0.75mmol of l-ornithine compared to the control group. In Experiment 2, the effect of orally administered l-ornithine (0 and 0.75mmol/10ml/kg, p.o.) on endogenous monoamine release was investigated using in vivo microdialysis. Only the monoamines metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and homovallinic acids (HVA) were detected in the present study. Dialysate concentrations of 5-HIAA, DOPAC and HVA were not significantly changed immediately after administration of l-ornithine and restraint stress. In conclusion, changes of corticosterone concentrations by orally administered l-ornithine were not related to alterations in brain monoamine metabolisms.