Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety

• DOI: 10.1126/science.adt0773
• Publication Date: 2025-03-27T18:00:27Z
• Authors: Zhenggang Zhu; Rong Gong; Vicente Rodriguez; Kathleen T. Quach; Xinyu Chen; Scott M. Sternson

Hedonic eating is defined as food consumption driven by palatability without physiological need. However, neural control of palatable food intake is poorly understood. We discovered that hedonic eating is controlled by a neural pathway from the peri–locus ceruleus to the ventral tegmental area (VTA). Using photometry-calibrated optogenetics, we found that VTA dopamine (VTA DA ) neurons encode palatability to bidirectionally regulate hedonic food consumption. VTA DA neuron responsiveness was suppressed during food consumption by semaglutide, a glucagon-like peptide receptor 1 (GLP-1R) agonist used as an antiobesity drug. Mice recovered palatable food appetite and VTA DA neuron activity during repeated semaglutide treatment, which was reversed by consumption-triggered VTA DA neuron inhibition. Thus, hedonic food intake activates VTA DA neurons, which sustain further consumption, a mechanism that opposes appetite reduction by semaglutide.