Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding

Jonathan D. Hommel, Richard Trinko, Robert M. Sears, Dan Georgescu, Zong Wu Liu, Xiao Bing Gao, Jeremy J. Thurmon, Michela Marinelli, Ralph J. DiLeone

Research output: Contribution to journalArticlepeer-review

655 Scopus citations


The leptin hormone is critical for normal food intake and metabolism. While leptin receptor (Lepr) function has been well studied in the hypothalamus, the functional relevance of Lepr expression in the ventral tegmental area (VTA) has not been investigated. The VTA contains dopamine neurons that are important in modulating motivated behavior, addiction, and reward. Here, we show that VTA dopamine neurons express Lepr mRNA and respond to leptin with activation of an intracellular JAK-STAT pathway and a reduction in firing rate. Direct administration of leptin to the VTA caused decreased food intake while long-term RNAi-mediated knockdown of Lepr in the VTA led to increased food intake, locomotor activity, and sensitivity to highly palatable food. These data support a critical role for VTA Lepr in regulating feeding behavior and provide functional evidence for direct action of a peripheral metabolic signal on VTA dopamine neurons.

Original languageEnglish (US)
Pages (from-to)801-810
Number of pages10
Issue number6
StatePublished - Sep 21 2006
Externally publishedYes



ASJC Scopus subject areas

  • General Neuroscience


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