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Published December 2011 | Accepted Version + Supplemental Material
Journal Article Open

Leptin regulates the reward value of nutrient


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.

Additional Information

© 2011 Nature Publishing Group. Received 13 January; accepted 11 October; published online 13 November 2011. We thank F. Pestilli for helping with the bootstrap analysis. We thank the Klarman Family Foundation for Eating Disorders (KFFfED) for supporting this work. A.I.D. was supported by Fundação para a Ciência e Tecnologia (Portugal) and KFFfED. J.V. was supported by KFFfED. X.R. and I.E.d.A. were supported by US National Institutes of Health grant DC009997 to I.E.d.A. F.Z., V.G. and K.D. were supported by the US National Institutes of Health (grant MH075957), the Gatsby Foundation and Defense Advanced Research Projects Agency. H.U.V. was partially supported by the Nancy M. and Samuel C. Fleming Research Scholar Award in Intercampus Collaborations. Author Contributions: A.I.D. contributed to all data. J.V. collected behavioral data. H.U.V. collected and analyzed the ofMRI data and generated the graphs and statistical parametric maps in Figure 1c,d. F.Z., V.G. and K.D. provided viral vectors. X.R. and I.E.d.A. contributed to Figure 2a. A.D., I.E.d.A. and J.F. wrote the manuscript.

Attached Files

Accepted Version - nihms-640177.pdf

Supplemental Material - nn.2977-S1.pdf


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