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

Abstract

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 3 mmol/10 ml/kg, p.o.), and restrained for 30 min from 30 min post administration. There was a significant decrease in the corticosterone levels in the group receiving 0.75 mmol of L-ornithine compared to the control group. In Experiment 2, the effect of orally administered L-ornithine (0 and 0.75 mmol/10 ml/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.

Antidepressant-like effects of paeoniflorin on the behavioural, biochemical, and neurochemical patterns of rats exposed to chronic unpredictable stress

“…Similarly, in experimental animals, chronic stress paradigms can recapitulate not only many behavioural characteristics but also a number of biochemical states of depression, including corticosterone and ACTH levels and neurochemical changes [1]. The results of this study showed that CUS caused significant reductions in the levels of 5-HT, NA, 5-HIAA and DA in rat brain, increases in the 5-HIAA/5-HT ratio in rat brain as well as increases in the levels of corticosterone and ACTH in rat serum, which are consistent with other studies [2][3][4][5]12]. The present study also showed that paeoniflorin treatment not only significantly increased the concentrations of NA, 5-HIAA and 5-HT and decreased the 5-HIAA/5-HT ratio in the CUS-induced rat brain but also decreased the serum corticosterone and ACTH levels.…”

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers

“…In addition, micro infusion of GABA agonists, such as the stress-derived neurosteroid tetrahydrodeoxycorticosterone (THDOC), into the paraventricular nucleus (PVN) decreased circulating levels of stress hormones [35]. Our result showing that orally administered L-ornithine decreased the serum cortisol level in human subjects was in agreement with previous animal studies on the effectiveness of stress reduction through the alleviation of HPA axis hyperactivity [20,31-34]. …”

“…That action was mediated by GABA A receptors. It was also confirmed that orally administered L-ornithine can be transported into the brain of mice [20], and as a result, reduced the plasma corticosterone concentration induced by restraint stress in mice. L-ornithine levels in the brain increased after oral administration of L-ornithine in mice [20].…”

“…A serotonin metabolite (5-hydroxyindole acetic acid, 5-HIAA) was induced in the striatum after L-ornithine supplementation [20]. Day-time serotonin levels stimulate production of melatonin during the night [50-52], therefore, L-ornithine might be considered an important nutrient to maintain the circadian rhythm and to allow individuals to sleep well.…”

“…Recently it was reported that orally administered L-ornithine reduced restraint stress-induced activation of the HPA axis in mice accompanied by a reduction in the serum corticosterone concentration [20]. It was shown that an intracerebroventricular (i.c.v.)…”