The role of GABAergic system on the inhibitory effect of ghrelin on food intake in neonatal chicks

Ghrelin is a gut-brain peptide that has a stimulatory effect on food intake in mammals. In contrast, this peptide decreases food intake in neonatal chicks when injected intracerebroventricularly (ICV). In mammals, neuropeptide Y (NPY) mediates the orexigenic effect of ghrelin whereas in chicks it appears that corticotrophin releasing factor (CRF) is partially involved in the inhibitory effect of ghrelin on food intake. Gamma aminobutyric acid (GABA) has a stimulatory effect on food intake in mammals and birds. In this study we investigated whether the anorectic effect of ghrelin is mediated by the GABAergic system. In Experiment 1, 3 h-fasted chicks were given an ICV injection of chicken ghrelin and picrotoxin, a GABAA receptors antagonist. Picrotoxin decreased food intake compared to the control chicks indicating a stimulatory effect of GABAA receptors on food intake. However, picrotoxin did not alter the inhibitory effect of ghrelin on food intake. In Experiment 2, THIP hydrochloride, a GABAA receptor agonist, was used in place of picrotoxin. THIP hydrochloride appeared to partially attenuate the decrease in food intake induced by ghrelin at 30 min postinjection. In Experiment 3, the effect of ICV injection of chicken ghrelin on gene expression of glutamate decarboxylase (GAD)1 and GAD2, GABA synthesis enzymes in the brain stem including hypothalamus, was investigated. The ICV injection of chicken ghrelin significantly reduced GAD2 gene expression. These findings suggest that ghrelin may decrease food intake in neonatal chicks by reducing GABA synthesis and thereby GABA release within brain feeding centers.

► Central ghrelin suppresses food intake in chicks.
► GABAergic system is a mechanism that may be involved in this inhibition.
► ICV effect of ghrelin on GAD1 and GAD2 mRNA expression was studied in the brainstem.
► GABA synthesis enzymes (GAD1 and GAD2) expression was decreased by chicken ghrelin.
► Ghrelin inhibits food intake in chicks by reducing the GABA content of brain stem.