Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France
Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France
Lucie P Pellissier
Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France; Biology and Bioinformatics of Signalling Systems, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Nouzilly, France
Yannick Corde
Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France
Florian Rebeillard
Cellular Biology and Molecular Pharmacology of central Receptors, Centre de Psychiatrie et Neurosciences, Inserm UMR_S894 - Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Maria Gallo
Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Barcelona, Spain
Christophe Gauthier
Biology and Bioinformatics of Signalling Systems, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Nouzilly, France
Audrey Léauté
Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France
Jorge Diaz
Cellular Biology and Molecular Pharmacology of central Receptors, Centre de Psychiatrie et Neurosciences, Inserm UMR_S894 - Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Anne Poupon
Biology and Bioinformatics of Signalling Systems, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Nouzilly, France
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U1258, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, France
Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U1258, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, France
Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U1258, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, France
GPR88 is an orphan G protein-coupled receptor (GPCR) considered as a promising therapeutic target for neuropsychiatric disorders; its pharmacology, however, remains scarcely understood. Based on our previous report of increased delta opioid receptor activity in Gpr88 null mice, we investigated the impact of GPR88 co-expression on the signaling of opioid receptors in vitro and revealed that GPR88 inhibits the activation of both their G protein- and β-arrestin-dependent signaling pathways. In Gpr88 knockout mice, morphine-induced locomotor sensitization, withdrawal and supra-spinal analgesia were facilitated, consistent with a tonic inhibitory action of GPR88 on µOR signaling. We then explored GPR88 interactions with more striatal versus non-neuronal GPCRs, and revealed that GPR88 can decrease the G protein-dependent signaling of most receptors in close proximity, but impedes β-arrestin recruitment by all receptors tested. Our study unravels an unsuspected buffering role of GPR88 expression on GPCR signaling, with intriguing consequences for opioid and striatal functions.