title: Leptin regulates the reward value of nutrient.
abstract: We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York, USA.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Domingos
authors.forename: Jake
authors.initials: J
authors.lastname: Vaynshteyn
authors.forename: Henning U
authors.initials: HU
authors.lastname: Voss
authors.forename: Xueying
authors.initials: X
authors.lastname: Ren
authors.forename: Viviana
authors.initials: V
authors.lastname: Gradinaru
authors.forename: Feng
authors.initials: F
authors.lastname: Zang
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Ivan E
authors.initials: IE
authors.lastname: de Araujo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Friedman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000075402:Channelrhodopsins; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D005502:Food; D005518:Food Preferences / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007834:Lasers; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008164:Luminescent Proteins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010100:Oxygen / Q000097:blood; D011506:Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D022661:RNA, Untranslated; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage / Q000031:analogs & derivatives; D013549:Sweetening Agents / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000098:blood supply / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
chemical_list: D000075402:Channelrhodopsins; D050483:Dopamine Plasma Membrane Transport Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D020738:Leptin; D008164:Luminescent Proteins; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D022661:RNA, Untranslated; D013549:Sweetening Agents; D013395:Sucrose; C026285:trichlorosucrose; D014446:Tyrosine 3-Monooxygenase; D010100:Oxygen
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