Reduced Ventral Tegmental Area GABA neuron output contributes to hyperactivity in the activity-based anorexia model in female mice
Nat Commun. 2025-12-24; :
DOI: 10.1038/s41467-025-67897-w
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https://www.bordeaux-neurocampus.fr/12396
Ducrocq F(1)(2), Delwel L(3), Papavoine N(3), Brouwer E(3), Kooij KL(3),
Wolterink-Donselaar IG(3), Drost L(3), Hak J(3), Veendijk M(3), Luijendijk
MCM(3), Meye FJ(#)(4), Adan RAH(#)(5)(6).
Author information:
(1)Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht
University, Utrecht, The Netherlands. .
(2)Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, Bordeaux, France.
.
(3)Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht
University, Utrecht, The Netherlands.
(4)Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht
University, Utrecht, The Netherlands. .
(5)Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht
University, Utrecht, The Netherlands. .
(6)Altrecht Eating Disorders Rintveld, Zeist, The Netherlands.
.
(#)Contributed equally
Anorexia nervosa (AN) has the highest mortality among psychiatric disorders,
with hyperactivity being one of the most persistent and deleterious symptoms.
Increased dopamine transmission is linked to AN and hyperactivity, though the
underlying mechanisms remain unclear. Local GABAergic neurons powerfully
regulate the dopamine system but their involvement in AN is unknown. Using the
activity-based anorexia (ABA) mouse model, we found that GABAergic transmission
onto ventral tegmental area dopamine (VTADA) neurons modulates hyperactivity in
female mice. Indeed, female mice exposed to the ABA model displayed higher
firing rates in VTADA compared to controls, along with reduced GABAergic
transmission onto VTADA cells and decreased excitability of VTAGABA neurons.
Chemogenetic stimulation of GABA neurons excitability in the midbrain reduced
hyperactivity and body weight loss in ABA mice, while reducing GABA neuron
activity worsened this phenotype. In summary, decreased GABAergic control over
VTA dopamine neurons contributes to development of hyperactivity in the ABA
model.
© 2025. The Author(s).
DOI: 10.1038/s41467-025-67897-w
PMID: 41444479
Conflict of interest statement: Competing interests: The authors declare no
competing interests.