Fiche publication
Date publication
janvier 2025
Journal
Addiction biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DARCQ Emmanuel
Tous les auteurs :
Lovelock DF, Liu W, Hamida SB, Cordero VL, Van Voorhies KJ, Martin M, Olmo IG, Darcq E, Rahman MT, Naassila M, Kieffer BL, Jin C, Besheer J
Lien Pubmed
Résumé
GPR88, an orphan G protein-coupled receptor primarily expressed in the striatum, has emerged as a potential target for treating alcohol use disorder (AUD) due to its role in modulating reward and motivational pathways. In this study, we investigated the effects of the GPR88 agonist RTI-122 on alcohol intake and motivation to self-administer alcohol under different conditions. In mice, RTI-122 reduced alcohol consumption in a two-bottle choice paradigm, which was prevented by Gpr88 knockout, confirming a GPR88-specific effect on the attenuation of alcohol drinking. In rats, RTI-122 dose-dependently reduced operant alcohol self-administration and decreased motivation to self-administer alcohol in progressive ratio tasks, regardless of whether the alcohol was adulterated with quinine or not. Additionally, a high dose of RTI-122 reduced yohimbine-induced reinstatement. Importantly, RTI-122 did not affect water intake in mice or sucrose self-administration in rats, indicating receptor- and reward-specific modulation of alcohol intake. These findings suggest that RTI-122, through GPR88 agonism, effectively reduces alcohol consumption and motivation across various contexts, positioning it as a promising lead for the development of new AUD treatments.
Mots clés
Animals, Motivation, drug effects, Receptors, G-Protein-Coupled, agonists, Mice, Male, Self Administration, Rats, Alcohol Drinking, drug therapy, Ethanol, administration & dosage, Conditioning, Operant, drug effects, Reward, Mice, Inbred C57BL, Yohimbine, pharmacology, Mice, Knockout, Quinine, pharmacology
Référence
Addict Biol. 2025 ;30(6):e70058
