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

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) neurons encode palatability to bidirectionally regulate hedonic food consumption. VTAneuron 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 VTAneuron activity during repeated semaglutide treatment, which was reversed by consumption-triggered VTAneuron inhibition. Thus, hedonic food intake activates VTAneurons, which sustain further consumption, a mechanism that opposes appetite reduction by semaglutide.