Dopamine D2 receptors in WFS1-neurons regulate food-seeking and avoidance behaviors

Laia Castell, Valentine Le Gall, Laura Cutando, Chloé P. Petit, Emma Puighermanal, Leila Makrini-Maleville, Ha Rang Kim, Daniel Jercog, Pauline Tarot, Adrien Tassou, Anne Gabrielle Harrus, Marcelo Rubinstein, Régis Nouvian, Cyril Rivat, Antoine Besnard, Pierre Trifilieff, Giuseppe Gangarossa, Patricia H. Janak, Cyril Herry, Emmanuel Valjent

Research output: Contribution to journalArticlepeer-review

Abstract

The selection and optimization of appropriate adaptive responses depends on interoceptive and exteroceptive stimuli as well as on the animal's ability to switch from one behavioral strategy to another. Although growing evidence indicate that dopamine D2R-mediated signaling events ensure the selection of the appropriate strategy for each specific situation, the underlying neural circuits through which they mediate these effects are poorly characterized. Here, we investigated the role of D2R signaling in a mesolimbic neuronal subpopulation expressing the Wolfram syndrome 1 (Wfs1) gene. This subpopulation is located within the nucleus accumbens, the central amygdala, the bed nucleus of the stria terminalis, and the tail of the striatum, all brain regions critical for the regulation of emotions and motivated behaviors. Using a mouse model carrying a temporally controlled deletion of D2R in WFS1-neurons, we demonstrate that intact D2R signaling in this neuronal population is necessary to regulate homeostasis-dependent food-seeking behaviors in both male and female mice. In addition, we found that reduced D2R signaling in WFS1-neurons impaired active avoidance learning and innate escape responses. Collectively, these findings identify a yet undocumented role for D2R signaling in WFS1-neurons as a novel effector through which dopamine optimizes appetitive behaviors and regulates defensive behaviors.

Original languageEnglish (US)
Article number110883
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume129
DOIs
StatePublished - Feb 8 2024

Keywords

  • Dopamine
  • Extended amygdala
  • Motivated behaviors
  • Neural circuit

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Fingerprint

Dive into the research topics of 'Dopamine D2 receptors in WFS1-neurons regulate food-seeking and avoidance behaviors'. Together they form a unique fingerprint.

Cite this