title: Orexin A-induced anxiety-like behavior is mediated through GABA-ergic, α- and β-adrenergic neurotransmissions in mice.
abstract: Orexins are hypothalamic neuropeptides, which are involved in several physiological functions of the central nervous system, including anxiety and stress. Several studies provide biochemical and behavioral evidence about the anxiogenic action of orexin A. However, we have little evidence about the underlying neuromodulation. Therefore, the aim of the present study was to investigate the involvement of neurotransmitters in the orexin A-induced anxiety-like behavior in elevated plus maze (EPM) test in mice. Accordingly, mice were pretreated with a non-selective muscarinic cholinergic antagonist, atropine; a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; a non-specific nitric oxide synthase (NOS) inhibitor, nitro-l-arginine; a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol 30min prior to the intracerebroventricular administration of orexin A. The EPM test started 30min after the i.c.v. injection of the neuropeptide. Our results show that orexin A decreases significantly the time spent in the arms (open/open+closed) and this action is reversed by bicuculline, phenoxybenzamine and propranolol, but not by atropine, haloperidol or nitro-l-arginine. Our results provide evidence for the first time that the orexin A-induced anxiety-like behavior is mediated through GABA-A-ergic, α- and β-adrenergic neurotransmissions, whereas muscarinic cholinergic, dopaminergic and nitrergic neurotransmissions may not be implicated.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Palotai
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary; Neuroscience Research Group of the Hungarian Academy of Sciences, Szeged, Hungary. Electronic address: telegdy.gyula@med.u-szeged.hu.
authors.forename: Gyula
authors.initials: G
authors.lastname: Telegdy
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Jászberényi
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D001285:Atropine / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000008:administration & dosage; D006220:Haloperidol / Q000008:administration & dosage; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D051379:Mice; D009479:Neuropeptides / Q000008:administration & dosage*; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D000068797:Orexins; D010643:Phenoxybenzamine / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D010643:Phenoxybenzamine; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D011433:Propranolol; D006220:Haloperidol; D001640:Bicuculline
keywords: Anxiety; Elevated plus maze; Neurotransmitter; Orexin A; Receptor antagonist