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Anxiolytic effect of the GPR103 receptor agonist peptide P550 (homolog of neuropeptide 26RFa) in mice. Involvement of neurotransmitters
Affiliation:1. Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary;2. Neuroscience Research Group of the Hungarian Academy of Sciences, Szeged, Hungary;1. Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham and Women''s Hospital and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA;2. School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Republic of Ireland;3. Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, University of Göteborg, Sahlgrenska University Hospital, Mölndal, Sweden;4. Wyatt Technology Corporation, Woburn, MA, USA;5. Massachusetts General Hospital and Harvard Medical School, Massachusetts General Institute for Neurodegenerative Disease, Charlestown, MA, USA;1. Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110, United States;2. Department of Internal Medicine, Divsion of Biostatistics, Washington University School of Medicine, Saint Louis, MO 63110, United States;3. Department of Internal Medicine, Division of Nutritional Science, Washington University School of Medicine, Saint Louis, MO 63110, United States;1. Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil;2. Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, Seropedica 23890-000, Brazil;1. Department of Physiology, Louisiana State University Health Sciences Center-New Orleans, New Orleans, LA 70112, United States;2. Joint Diabetes, Endocrinology & Metabolism Program, Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States;1. Department of Physiology, Chonbuk National University Medical School, Jeonju 560-180, Republic of Korea;2. Department of Surgery, Chonbuk National University Medical School, Jeonju 560-180, Republic of Korea;3. Department of Internal Medicine, Yanbian University, China
Abstract:The GPR103 receptor is a G protein-coupled receptor, which plays a role in several physiological functions. However, the role of the GPR103 receptor in anxiety has not been clarified. The first aim of our study was to elucidate the involvement of the GPR103 receptor in anxious behavior. Mice were treated with peptide P550, which is the mouse homolog of neuropeptide 26RFa and has similar activity for the GPR103 receptor as neuropeptide 26RFa. The anxious behavior was investigated using an elevated plus-maze paradigm. The second aim of our study was to investigate the underlying neurotransmissions. Accordingly, mice were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a γ-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a nonselective β-adrenergic receptor antagonist, propranolol. Our results demonstrated that peptide P550 reduces anxious behavior in elevated plus maze test in mice. Our study shows also that GABAA-ergic, α- and β-adrenergic transmissions are all involved in this action, whereas 5-HT1 and 5-HT2 serotonergic, muscarinic cholinergic and D2, D3, D4 dopaminergic mechanisms may not be implicated.
Keywords:GPR103  Anxiety  Elevated plus maze  Neurotransmitter  Receptor antagonist
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