The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events

Reward processes have traditionally been ascribed to dopamine (DA)-associated circuits. While external stimuli, such as food and drugs of abuse, are activators of DA-neuron activity, growing evidence indicates that interoceptive signals also play a critical role. Among these, the gut-brain vagal axis has emerged as a key regulator, although its precise contribution to mesolimbic DA signaling and behavior remains unclear. Here, we combine complementary ex vivo and in vivo approaches across multiple scales to show that gut-brain vagal tone is essential for gating mesolimbic DA system activity and functions, modulating DA-dependent molecular and cellular processes, and scaling both food- and drug-induced reinforcement. These findings challenge the traditional brain-centric view of reward processing, supporting a more integrated model in which vagus-mediated interoceptive signals intrinsically shape motivation and reinforcement. By uncovering the influence of gut-brain vagal communication on DA functions, this work provides insights into the neurobiology of adaptive and maladaptive reward, with broad relevance for eating disorders and addiction.

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Publication Details

Journal
Science Advances
Published
2026-01-30
DOI
https://doi.org/10.1126/sciadv.adz0828
Primary Topic
Neurotransmitter Receptor Influence on Behavior
Type
article
Field-Weighted Citation Impact
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article

The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events

Tinaïg Le Borgne, Laurent Venance, Julien Castel, Camille de Almeida et al.
Science Advances
Neurotransmitter Receptor Influence on Behavior
article

The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events

Tinaïg Le Borgne, Laurent Venance, Julien Castel, Camille de Almeida, Sylvie Pérez, Linh‐Chi Bui, Marie Vandecasteele, Anthony Ansoult, Giuseppe Gangarossa, Nicolas Heck, Fabio Marti, Faustine Arrivet, Serge Luquet, Benoit Bertrand, Nejmeh Mashhour, Oriane Onimus
article en

Abstract

Reward processes have traditionally been ascribed to dopamine (DA)-associated circuits. While external stimuli, such as food and drugs of abuse, are activators of DA-neuron activity, growing evidence indicates that interoceptive signals also play a critical role. Among these, the gut-brain vagal axis has emerged as a key regulator, although its precise contribution to mesolimbic DA signaling and behavior remains unclear. Here, we combine complementary ex vivo and in vivo approaches across multiple scales to show that gut-brain vagal tone is essential for gating mesolimbic DA system activity and functions, modulating DA-dependent molecular and cellular processes, and scaling both food- and drug-induced reinforcement. These findings challenge the traditional brain-centric view of reward processing, supporting a more integrated model in which vagus-mediated interoceptive signals intrinsically shape motivation and reinforcement. By uncovering the influence of gut-brain vagal communication on DA functions, this work provides insights into the neurobiology of adaptive and maladaptive reward, with broad relevance for eating disorders and addiction.

Science AdvancesVol. 12(5)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Institut Universitaire de France (FR), Collège de France (FR), Université Paris Cité (FR), Université Paris Sciences et Lettres (FR), Sorbonne Université (FR), Institut de Biologie Paris-Seine (FR), Centre Interdisciplinaire de Recherche en Biologie (FR), Laboratoire Plasticité du Cerveau (FR), Unit of Functional and Adaptive Biology (FR), ESPCI Paris (FR)
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