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Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine’s rewarding effects but preserves natural reward processing

dc.rights.licenseopenen_US
hal.structure.identifierNeuroscience Paris Seine [NPS]
dc.contributor.authorANDRIANARIVELO, Andry
hal.structure.identifierNeuroscience Paris Seine [NPS]
dc.contributor.authorSAINT-JOUR, Estefani
hal.structure.identifierInstitut de pharmacologie moléculaire et cellulaire [IPMC]
dc.contributor.authorPOUSINHA, Paula
hal.structure.identifierInstitut de pharmacologie moléculaire et cellulaire [IPMC]
dc.contributor.authorFERNANDEZ, Sebastian P.
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorPETITBON, Anna
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorDE SMEDT-PEYRUSSE, Veronique
hal.structure.identifierNeuroscience Paris Seine [NPS]
dc.contributor.authorHECK, Nicolas
dc.contributor.authorORTIZ, Vanesa
dc.contributor.authorALLICHON, Marie-Charlotte
dc.contributor.authorKAPPÈS, Vincent
dc.contributor.authorBETUING, Sandrine
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorWALLE, Roman
dc.contributor.authorZHU, Ying
dc.contributor.authorJOSEPHINE, Charlene
hal.structure.identifierCommissariat à l'énergie atomique et aux énergies alternatives [CEA]
dc.contributor.authorBEMELMANS, Alexis-Pierre
dc.contributor.authorTURECKI, Gustavo
dc.contributor.authorMECHAWAR, Naguib
dc.contributor.authorJAVITCH, Jonathan A.
dc.contributor.authorCABOCHE, Jocelyne
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorTRIFILIEFF, Pierre
dc.contributor.authorBARIK, Jacques
dc.contributor.authorVANHOUTTE, Peter
dc.date.accessioned2023-06-09T08:20:47Z
dc.date.available2023-06-09T08:20:47Z
dc.date.issued2021-10-20
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182609
dc.description.abstractEnAddictive drugs increase dopamine in the nucleus accumbens (NAc), where it persistently shapes excitatory glutamate transmission and hijacks natural reward processing. Here, we provide evidence, from mice to humans, that an underlying mechanism relies on drug-evoked heteromerization of glutamate N-methyl-d-aspartate receptors (NMDAR) with dopamine receptor 1 (D1R) or 2 (D2R). Using temporally controlled inhibition of D1R-NMDAR heteromerization, we unraveled their selective implication in early phases of cocaine-mediated synaptic, morphological, and behavioral responses. In contrast, preventing D2R-NMDAR heteromerization blocked the persistence of these adaptations. Interfering with these heteromers spared natural reward processing. Notably, we established that D2R-NMDAR complexes exist in human samples and showed that, despite a decreased D2R protein expression in the NAc, individuals with psychostimulant use disorder display a higher proportion of D2R forming heteromers with NMDAR. These findings contribute to a better understanding of molecular mechanisms underlying addiction and uncover D2R-NMDAR heteromers as targets with potential therapeutic value.
dc.description.sponsorshipContribution des astrocytes aux ondulations hippocampiquesen_US
dc.description.sponsorshipCibler les complexes formés par les récepteurs de la dopamine et du glutamate pour atténuer les pathologies liées au stress - ANR-18-CE37-0003en_US
dc.description.sponsorshipInitiative d'excellence de l'Université de Bordeauxen_US
dc.description.sponsorshipContribution d'un état hypodopaminergique dorsostriatal dans le développement de l'usage compulsif d'alcool : Implication pour les mécanismes physiopathologiques de l'alcoolodépendance - ANR-16-CE16-0002en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.title.enDisrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine’s rewarding effects but preserves natural reward processing
dc.typeArticle de revueen_US
dc.identifier.doi10.1126/sciadv.abg5970en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
bordeaux.journalScience Advancesen_US
bordeaux.pageeabg5970en_US
bordeaux.volume7en_US
bordeaux.hal.laboratoriesNutriNeuro (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue43en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDCentre National de la Recherche Scientifiqueen_US
bordeaux.identifier.funderIDInstitut National de la Santé et de la Recherche Médicaleen_US
bordeaux.identifier.funderIDInstitut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnementen_US
hal.exportfalse
dc.rights.ccCC BY-NCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Science%20Advances&rft.date=2021-10-20&rft.volume=7&rft.issue=43&rft.spage=eabg5970&rft.epage=eabg5970&rft.au=ANDRIANARIVELO,%20Andry&SAINT-JOUR,%20Estefani&POUSINHA,%20Paula&FERNANDEZ,%20Sebastian%20P.&PETITBON,%20Anna&rft.genre=article


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