title: Agrp neuron activity is required for alcohol-induced overeating.
abstract: Alcohol intake associates with overeating in humans. This overeating is a clinical concern, but its causes are puzzling, because alcohol (ethanol) is a calorie-dense nutrient, and calorie intake usually suppresses brain appetite signals. The biological factors necessary for ethanol-induced overeating remain unclear, and societal causes have been proposed. Here we show that core elements of the brain's feeding circuits-the hypothalamic Agrp neurons that are normally activated by starvation and evoke intense hunger-display electrical and biochemical hyperactivity on exposure to dietary doses of ethanol in brain slices. Furthermore, by circuit-specific chemogenetic interference in vivo, we find that the Agrp cell activity is essential for ethanol-induced overeating in the absence of societal factors, in single-housed mice. These data reveal how a widely consumed nutrient can paradoxically sustain brain starvation signals, and identify a biological factor required for appetite evoked by alcohol.
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cains
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Blomeley
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6BT, UK.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Kollo
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: Romeo
authors.initials: R
authors.lastname: Rácz
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.|Institute of Psychiatry, Psychology and Neuroscience, Department of Developmental Neurobiology, King's College London, London WC2R 2LS, UK.
authors.forename: Denis
authors.initials: D
authors.lastname: Burdakov
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004435:Eating / Q000187:drug effects; D004594:Electrophysiology / Q000379:methods; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006963:Hyperphagia / Q000139:chemically induced* / Q000473:pathology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D059010:Single-Cell Analysis / Q000379:methods
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D000431:Ethanol