Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure

Roman Walle (), Anna Petitbon, Giulia R. Fois, Christophe Varin, Enrica Montalban, Lola Hardt, Andrea Contini, Maria Florencia Angelo, Mylène Potier, Rodrigue Ortole, Asma Oummadi, Véronique Smedt-Peyrusse, Roger A. Adan, Bruno Giros, Francis Chaouloff, Guillaume Ferreira, Alban Kerchove d’Exaerde, Fabien Ducrocq, François Georges and Pierre Trifilieff ()
Additional contact information
Roman Walle: NutriNeuro
Anna Petitbon: NutriNeuro
Giulia R. Fois: UMR5293 F-33000
Christophe Varin: ULB Neuroscience Institute, WELBIO, Université Libre de Bruxelles (ULB)
Enrica Montalban: NutriNeuro
Lola Hardt: NutriNeuro
Andrea Contini: NutriNeuro
Maria Florencia Angelo: NutriNeuro
Mylène Potier: NutriNeuro
Rodrigue Ortole: NutriNeuro
Asma Oummadi: NutriNeuro
Véronique Smedt-Peyrusse: NutriNeuro
Roger A. Adan: University Medical Center Utrecht, Universiteitsweg 100
Bruno Giros: Douglas Hospital, McGill University
Francis Chaouloff: NeuroCentre INSERM U1215
Guillaume Ferreira: NutriNeuro
Alban Kerchove d’Exaerde: ULB Neuroscience Institute, WELBIO, Université Libre de Bruxelles (ULB)
Fabien Ducrocq: NutriNeuro
François Georges: UMR5293 F-33000
Pierre Trifilieff: NutriNeuro

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Accumulating evidence points to dysregulations of the Nucleus Accumbens (NAc) in eating disorders (ED), however its precise contribution to ED symptomatic dimensions remains unclear. Using chemogenetic manipulations in male mice, we found that activity of dopamine D1 receptor-expressing neurons of the NAc core subregion facilitated effort for a food reward as well as voluntary exercise, but decreased food intake, while D2-expressing neurons have opposite effects. These effects are congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure, whilst the opposite manipulations favored energy intake. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.

Date: 2024
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DOI: 10.1038/s41467-024-46874-9

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