ANDRIANARIVELO, Andry; SAINT-JOUR, Estefani; POUSINHA, Paula; FERNANDEZ, Sebastian P.; PETITBON, Anna; DE SMEDT-PEYRUSSE, Veronique; HECK, Nicolas; ORTIZ, Vanesa; ALLICHON, Marie-Charlotte; KAPPÈS, Vincent; BETUING, Sandrine; WALLE, Roman; ZHU, Ying; JOSEPHINE, Charlene; BEMELMANS, Alexis-Pierre; TURECKI, Gustavo; MECHAWAR, Naguib; JAVITCH, Jonathan A.; CABOCHE, Jocelyne; TRIFILIEFF, Pierre; BARIK, Jacques; VANHOUTTE, Peter

doi:10.1126/sciadv.abg5970

ANDRIANARIVELO, Andry
Neuroscience Paris Seine [NPS]

SAINT-JOUR, Estefani
Neuroscience Paris Seine [NPS]

POUSINHA, Paula
Institut de pharmacologie moléculaire et cellulaire [IPMC]

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Science Advances. 2021-10-20, vol. 7, n° 43, p. eabg5970

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Addictive 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.< Leer menos

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https://oskar-bordeaux.fr/handle/20.500.12278/182609

DOI

http://dx.doi.org/10.1126/sciadv.abg5970

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Contribution des astrocytes aux ondulations hippocampiques
Cibler les complexes formés par les récepteurs de la dopamine et du glutamate pour atténuer les pathologies liées au stress - ANR-18-CE37-0003
Initiative d'excellence de l'Université de Bordeaux - ANR-10-IDEX-0003
Contribution d'un état hypodopaminergique dorsostriatal dans le développement de l'usage compulsif d'alcool : Implication pour les mécanismes physiopathologiques de l'alcoolodépendance - ANR-16-CE16-0002

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NutriNeuro (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286

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

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