CAST Web News | Fall 2025
Cocaine use disorder (CUD) remains a critical public health challenge in the United States, with no FDA-approved medications currently available to improve treatment outcomes. Two innovative research projects are paving the way for potential breakthroughs by focusing on unique brain receptors involved in addiction pathways.
Project 1: Exploring GPR6 as a Therapeutic Target
Grant: R21DA063306
Principal Investigators: Kathryn Cunningham and John Allen
This project investigates the orphan G protein-coupled receptor GPR6, which is predominantly expressed in neurons within CUD-related neurocircuitry. By elucidating the role of GPR6 across neurobiological and behavioral dimensions, researchers aim to uncover new strategies for therapeutic intervention. The findings could lead to novel approaches for addressing the complex mechanisms underlying cocaine addiction.
Project 2: Developing GPR52 Activators for Addiction Treatment
Grant: R01DA060228
Principal Investigators: John Allen and Jia Zhou
In parallel, this study focuses on creating small molecule activators of GPR52, another brain receptor implicated in addiction. Researchers will evaluate whether these compounds can reduce cocaine-taking or cocaine-seeking behaviors in preclinical models. Success in this area could open the door to investigational treatments for substance use disorders and related neuropsychiatric conditions.
Why It Matters:
Both projects represent cutting-edge efforts to identify and validate new molecular targets for CUD treatment. By advancing our understanding of GPR6 and GPR52, these studies aim to transform addiction therapy and improve outcomes for individuals struggling with cocaine dependence.