L-ORNITHINE ATTENUATES CORTICOTROPIN-RELEASING FACTOR-INDUCED STRESS RESPONSES ACTING AT GABAA RECEPTORS IN NEONATAL CHICKS

I.c.v. injection of L-ornithine has been shown to have sedative and hypnotic effects on neonatal chicks exposed to acute stressful conditions. To clarify the mechanism, we conducted three experiments under strengthened stressful conditions with corticotropin-releasing factor (CRF). In Experiment 1, the effect of i.c.v. injection of CRF, L-ornithine (0.5 mu mol) or CRF with L-ornithine on the stressful response of chicks was investigated. Compared with the vehicle control, CRF increased distress vocalizations and the time spent in active wakefulness. L-Ornithine increased the time spent in sleeping posture, even following stimulation with CRF. In Experiment 2, dose-dependent effects of L-ornithine were investigated using i.c.v. administration with vehicle, CRF alone or CRF plus L-ornithine (0.125, 0.25 or 0.5 mu mol). L-Ornithine decreased the CRF-stimulated distress vocalizations in a dose-dependent manner. In Experiment 3, the chicks were injected i.c.v. with either CRF, CRF plus L-ornithine (0.5 mu mol), CRF plus the gamma-aminobutyric acid (GABA)(A) receptor antagonist picrotoxin or L-ornithine with picrotoxin. The sedative and hypnotic effects induced by L-ornithine were blocked with co-administration of picrotoxin. These results suggest that L-ornithine could attenuate CRF-stimulated stress behaviors acting at GABA(A) receptors. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.