Vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice.

Couty P(1), Yung S(2), Dulapt I(2), Berger L(2), Santoro A(2), Hardt L(2), Petitbon A(2), Ducrocq F(2), Walle R(2), Catanese J(2), Alfos S(2), Helbling JC(2), Angelo MF(2), Sabran C(3), Borel P(3), Ferreira G(2), Bosch-Bouju C(2), Trifilieff P(#)(4), Touyarot K(#)(2).

Author information:
(1)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro Lab, Bordeaux, France.
.
(2)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro Lab, Bordeaux, France.
(3)C2VN, Aix Marseille Univ., INRAE, INSERM, Marseille, France.
(4)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro Lab, Bordeaux, France.
.
(#)Contributed equally

Neurodevelopmental psychiatric diseases such as schizophrenia or affective
disorders share common symptomatic dimensions, in particular reward processing
dysfunctions, associated with dysregulation of dopamine (DA) transmission.
Retinoic acid (RA) homeostasis, the active metabolite of vitamin A, is altered
across psychiatric disorders but whether impaired developmental RA signaling
impacts the functionality of DA-related reward processing at adulthood remains
poorly explored. Herein, we found that vitamin A (i.e., retinol) deficiency
(VAD) from gestation to adulthood potentiates instrumental responding in
motivational tasks and increases choice impulsivity in male, but not female
mice. These behavioral alterations in males are coherent with reduced DA
transporter (DAT) expression in the midbrain and increased mesolimbic DA
dynamics associated with instrumental responding. In accordance, chemogenetic
inhibition of midbrain DA neurons normalizes motivational performance in VAD
males. Our results support that developmental VAD induces sex-specific reward
processing alterations at adulthood through hyperactivity of the mesolimbic DA
pathway. Such findings reinforce the idea that RA signaling is an important
modulator of the brain reward system by shaping DA transmission.

© 2026. The Author(s), under exclusive licence to American College of
Neuropsychopharmacology.

DOI: 10.1038/s41386-026-02400-7
PMID: 41935220

Conflict of interest statement: Competing interests: The authors declare no
competing interests.

Auteurs Bordeaux Neurocampus