title: Endogenous central amygdala mu-opioid receptor signaling promotes sodium appetite in mice.
abstract: Due to the importance of dietary sodium and its paucity within many inland environments, terrestrial animals have evolved an instinctive sodium appetite that is commensurate with sodium deficiency. Despite a well-established role for central opioid signaling in sodium appetite, the endogenous influence of specific opioid receptor subtypes within distinct brain regions remains to be elucidated. Using selective pharmacological antagonists of opioid receptor subtypes, we reveal that endogenous mu-opioid receptor (MOR) signaling strongly drives sodium appetite in sodium-depleted mice, whereas a role for kappa (KOR) and delta (DOR) opioid receptor signaling was not detected, at least in sodium-depleted mice. Fos immunohistochemistry revealed discrete regions of the mouse brain displaying an increased number of activated neurons during sodium gratification: the rostral portion of the nucleus of the solitary tract (rNTS), the lateral parabrachial nucleus (LPB), and the central amygdala (CeA). The CeA was subsequently targeted with bilateral infusions of the MOR antagonist naloxonazine, which significantly reduced sodium appetite in mice. The CeA is therefore identified as a key node in the circuit that contributes to sodium appetite. Moreover, endogenous opioids, acting via MOR, within the CeA promote this form of appetitive behavior.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia.|The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia.|School of Medicine, Deakin University, Geelong, VIC 3216, Australia.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Smith
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia.
authors.forename: Lesley L
authors.initials: LL
authors.lastname: Walker
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia.|Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors.forename: Tanawan
authors.initials: T
authors.lastname: Leeboonngam
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia.|Department of Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3052, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKinley
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia; Andrew.Lawrence@florey.edu.au ddenton@unimelb.edu.au.|Office of the Dean, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3052, Australia.|Baker IDI (International Diabetes Institute) Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Denton
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia; Andrew.Lawrence@florey.edu.au ddenton@unimelb.edu.au.|The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D001931:Brain Mapping; D066274:Central Amygdaloid Nucleus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009474:Neurons / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D012982:Sodium, Dietary / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D012982:Sodium, Dietary; D009270:Naloxone; C034643:naloxonazine
keywords: central amygdala; mu-opioid receptor; sodium appetite