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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.

Original publication

DOI

10.1038/nn.2977

Type

Journal article

Journal

Nat Neurosci

Publication Date

13/11/2011

Volume

14

Pages

1562 - 1568

Keywords

Analysis of Variance, Animals, Channelrhodopsins, Choice Behavior, Dopamine Plasma Membrane Transport Proteins, Dose-Response Relationship, Drug, Drinking Behavior, Fasting, Food, Food Preferences, Gene Expression Regulation, Image Processing, Computer-Assisted, Lasers, Leptin, Luminescent Proteins, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Oxygen, Proteins, Proto-Oncogene Proteins c-fos, RNA, Untranslated, Reward, Sucrose, Sweetening Agents, Tyrosine 3-Monooxygenase, Ventral Tegmental Area