PMID- 37858736 OWN - NLM STAT- MEDLINE DCOM- 20231227 LR - 20231227 IS - 1878-4216 (Electronic) IS - 0278-5846 (Linking) VI - 129 DP - 2024 Feb 8 TI - Dopamine D2 receptors in WFS1-neurons regulate food-seeking and avoidance behaviors. PG - 110883 LID - S0278-5846(23)00169-0 [pii] LID - 10.1016/j.pnpbp.2023.110883 [doi] AB - 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. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Castell, Laia AU - Castell L AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France; Department of Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: lcastel9@jh.edu. FAU - Le Gall, Valentine AU - Le Gall V AD - Universite, Bordeaux, Neurocentre Magendie, U1215, Bordeaux F-33077, France. FAU - Cutando, Laura AU - Cutando L AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France. FAU - Petit, Chloe P AU - Petit CP AD - INM, Universite, Montpellier, Inserm, Montpellier F-34000, France. FAU - Puighermanal, Emma AU - Puighermanal E AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France. FAU - Makrini-Maleville, Leila AU - Makrini-Maleville L AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France. FAU - Kim, Ha-Rang AU - Kim HR AD - Universite, Bordeaux, Neurocentre Magendie, U1215, Bordeaux F-33077, France. FAU - Jercog, Daniel AU - Jercog D AD - Universite, Bordeaux, Neurocentre Magendie, U1215, Bordeaux F-33077, France. FAU - Tarot, Pauline AU - Tarot P AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France. FAU - Tassou, Adrien AU - Tassou A AD - INM, Universite, Montpellier, Inserm, Montpellier F-34000, France. FAU - Harrus, Anne-Gabrielle AU - Harrus AG AD - INM, Universite, Montpellier, Inserm, Montpellier F-34000, France. FAU - Rubinstein, Marcelo AU - Rubinstein M AD - Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular, CONICET; FCEN, Universidad de Buenos Aires, Buenos Aires, Argentina; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Nouvian, Regis AU - Nouvian R AD - INM, Universite, Montpellier, Inserm, Montpellier F-34000, France. FAU - Rivat, Cyril AU - Rivat C AD - INM, Universite, Montpellier, Inserm, Montpellier F-34000, France. FAU - Besnard, Antoine AU - Besnard A AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France. FAU - Trifilieff, Pierre AU - Trifilieff P AD - Universite, Bordeaux, INRAE, Bordeaux INP, NutriNeuro, Bordeaux F-33000, France. FAU - Gangarossa, Giuseppe AU - Gangarossa G AD - Universite Paris Cite, CNRS, Unite de Biologie Fonctionnelle et Adaptative, Paris F-75013, France; Institut Universitaire de France, France. FAU - Janak, Patricia H AU - Janak PH AD - Department of Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA. FAU - Herry, Cyril AU - Herry C AD - Universite, Bordeaux, Neurocentre Magendie, U1215, Bordeaux F-33077, France. FAU - Valjent, Emmanuel AU - Valjent E AD - IGF, Universite, Montpellier, CNRS, Inserm, Montpellier F-34094, France. Electronic address: emmanuel.valjent@igf.cnrs.fr. LA - eng PT - Journal Article DEP - 20231017 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - VTD58H1Z2X (Dopamine) RN - 0 (Receptors, Dopamine D1) RN - 0 (Receptors, Dopamine D2) RN - 0 (DRD2 protein, mouse) SB - IM MH - Animals MH - Female MH - Male MH - Avoidance Learning MH - *Dopamine MH - Neurons/physiology MH - Receptors, Dopamine D1 MH - Receptors, Dopamine D2/genetics MH - *Wolfram Syndrome OTO - NOTNLM OT - Dopamine OT - Extended amygdala OT - Motivated behaviors OT - Neural circuit COIS- Declaration of Competing Interest None. EDAT- 2023/10/20 06:42 MHDA- 2023/12/19 06:42 CRDT- 2023/10/20 00:33 PHST- 2023/07/03 00:00 [received] PHST- 2023/10/09 00:00 [revised] PHST- 2023/10/16 00:00 [accepted] PHST- 2023/12/19 06:42 [medline] PHST- 2023/10/20 06:42 [pubmed] PHST- 2023/10/20 00:33 [entrez] AID - S0278-5846(23)00169-0 [pii] AID - 10.1016/j.pnpbp.2023.110883 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2024 Feb 8;129:110883. doi: 10.1016/j.pnpbp.2023.110883. Epub 2023 Oct 17.