Bicuculline, GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin after an acute stress

GASTÓN S.; CID M.P; SALVATIERRA N.A

BEHAVIOURAL BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2017 vol. 320 p. 464 - 472

0166-4328

Ghrelin is a peptide of 28 amino acids with homology between species. Ghrelin acts on the central nervous system to regulate different actions, including control of growth hormone secretion and metabolic regulation. It was suggested that central ghrelin is one such mediator of behaviors linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of forebrain was blocked by bicuculline (GABAA receptor competitive antagonist) but not by diazepam (GABAA receptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies indicate that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is yet unclear whether this effect of ghrelin could be associated with HPA activation. Therefore, we examined whether HPA activation mediates anxiety behavior induced by Ghr injected into the IMM through GABAA receptors of neonatal chick forebrain. In Open Field test, intraperitoneal bicuculline blocked the anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30 pmol) in neonatal chicks. In the present study, we showed for the first time that a competitive antagonist of GABAA receptor suppressed the HPA axis activation induced by an anxiogenic dose of ghrelin. These results show that the anxiogenic ghrelin action involves the activation of the HPA axis, with a complex functional interaction with the GABAA receptor.