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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年4月4日

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  • Pauline Couty,
  • Sonya Yung,
  • Ilona Dulapt,
  • Loreleï Berger,
  • Adrien Santoro,
  • Lola Hardt,
  • Anna Petitbon,
  • Fabien Ducrocq,
  • Roman Walle,
  • Julien Catanese,
  • Serge Alfos,
  • Jean-Christophe Helbling,
  • Maria-Florencia Angelo,
  • Charlotte Sabran,
  • Patrick Borel,
  • Guillaume Ferreira,
  • Clémentine Bosch-Bouju,
  • Pierre Trifilieff,
  • Katia Touyarot

摘要

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.