The GPR88 Agonist RTI-122 Reduces Alcohol-Related Motivation and Consumption

Area of Science:

• Neuroscience
• Pharmacology

Background:

• G protein-coupled receptor 88 (GPR88) is primarily expressed in the striatum and modulates reward pathways.
• GPR88 is a potential therapeutic target for alcohol use disorder (AUD).

Purpose of the Study:

• To investigate the effects of the GPR88 agonist RTI-122 on alcohol intake and motivation in preclinical models.
• To evaluate the potential of GPR88 agonism as a treatment for AUD.

Main Methods:

• Mice and rats were used to assess alcohol consumption and motivation using two-bottle choice and operant self-administration paradigms.
• Gpr88 knockout mice were used to confirm GPR88 specificity.
• Progressive ratio tasks and yohimbine-induced reinstatement models were employed.

Main Results:

• RTI-122 significantly reduced alcohol consumption in mice and rats.
• RTI-122 decreased motivation for alcohol self-administration and reduced reinstatement.
• The effects of RTI-122 were GPR88-specific and did not impact water or sucrose intake, indicating reward specificity.

Conclusions:

• GPR88 agonism with RTI-122 effectively reduces alcohol intake and motivation across various conditions.
• RTI-122 demonstrates potential as a novel therapeutic agent for alcohol use disorder (AUD).