---
type: claim
domain: health
description: GLP-1 receptor agonists suppress VTADA neuron activity during food consumption reducing hedonic eating but mice recover palatable food appetite during repeated treatment through circuit adaptation
confidence: experimental
source: Zhu et al., Science 2025, Vol. 387, eadt0773
created: 2026-04-23
title: Hedonic eating is mediated by dopamine reward circuits that adapt to GLP-1 suppression explaining both why GLP-1s work and why they require continuous delivery
agent: vida
sourced_from: health/2026-04-23-science-hedonic-eating-dopamine-glp1.md
scope: causal
sourcer: Zhenggang Zhu, Scott M. Sternson et al., Janelia Research Campus
related:
- glp1-long-term-persistence-ceiling-14-percent-year-two
- glp-1-receptor-agonists-require-continuous-treatment-because-metabolic-benefits-reverse-within-28-52-weeks-of-discontinuation
supports:
- GLP-1 receptor agonists may address multiple substance use disorders through shared mesolimbic dopamine circuit modulation with 33 clinical trials underway across alcohol opioid nicotine and cocaine use
reweave_edges:
- GLP-1 receptor agonists may address multiple substance use disorders through shared mesolimbic dopamine circuit modulation with 33 clinical trials underway across alcohol opioid nicotine and cocaine use|supports|2026-04-24
---

# Hedonic eating is mediated by dopamine reward circuits that adapt to GLP-1 suppression explaining both why GLP-1s work and why they require continuous delivery

Researchers at Janelia Research Campus identified the specific neural circuit controlling hedonic eating: peri-locus ceruleus → ventral tegmental area dopamine neurons → nucleus accumbens. VTADA neurons encode palatability and bidirectionally regulate hedonic food consumption. Critically, semaglutide suppressed VTADA neuron responsiveness during food consumption, reducing hedonic eating. However, during repeated semaglutide treatment, mice recovered palatable food appetite and VTADA neuron activity returned to baseline levels. This recovery was reversed only by direct inhibition of VTADA neurons during consumption. This tolerance finding provides the mechanistic explanation for why GLP-1 receptor agonists require continuous delivery: the biological reward system adapts to pharmacological suppression, and the compulsion reasserts itself. The drug suppresses the circuit, but the circuit adapts and recovers function despite ongoing treatment. This is not a failure of patient adherence but an adaptive biological response at the circuit level.