title: Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.
abstract: Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABAAreceptor competitive antagonist) but not by diazepam (a GABAAreceptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is still unclear whether this effect of ghrelin is associated with HPA activation. Therefore, we investigated whether anxiety behavior induced by intra-IMM ghrelin and mediated through GABAAreceptors could be associated with HPA axis activation in the neonatal chick. In the present study, in an Open Field test, intraperitoneal bicuculline methiodide blocked anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30pmol) in neonatal chicks. Moreover, we showed for the first time that a competitive antagonist of GABAAreceptor 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 GABAAreceptor.
authors: Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), UNC, CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, 5016 Córdoba, Argentina. Electronic address: solegaston@gmail.com.
authors: M S
authors: MS
authors: Gastón
authors: Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), UNC, CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, 5016 Córdoba, Argentina.
authors: M P
authors: MP
authors: Cid
authors: Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), UNC, CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, 5016 Córdoba, Argentina. Electronic address: nancy.salvatierra@unc.edu.ar.
authors: N A
authors: NA
authors: Salvatierra
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002645:Chickens; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D054439:Ghrelin / Q000627:therapeutic use*; D008297:Male; D011930:Reaction Time / Q000187:drug effects; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D058787:GABA-A Receptor Antagonists; D054439:Ghrelin; C017069:bicuculline methiodide; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D001640:Bicuculline
keywords: Adrenocorticotropic hormone; Anxiety-like behavior; Corticosterone; GABA(A) receptor; Ghrelin