Genetic Markers for Compulsive Cocaine Use Identified in Rats

A study published in Nature Communications by researchers at the University of California San Diego has identified genetic markers associated with compulsive cocaine use in rats, including a group of genes (Ces1) that produce an enzyme in the liver that metabolizes cocaine.

Key Findings

"Finding a liver-based enzyme that shapes cocaine-taking behavior was a real 'aha' moment for us."
— Olivier George, PhD, co-corresponding author

• The study used nearly 900 genetically diverse rats to map genetic markers linked to addiction-like behaviors.
• Researchers identified six major genetic regions related to escalation of drug intake and time between doses.
• The Ces1 genes, responsible for the enzyme that breaks down cocaine, were strongly associated with drug-taking behavior.
• The study also replicated a known genetic link in humans (Trak2), supporting cross-species relevance.

Methodology

The research team employed heterogeneous stock rats to mimic human genetic diversity. Behavioral studies measured the frequency and compulsivity of self-administration, while genetic analysis involved millions of markers per animal.

Expert Reactions

"Identifying those genes is an important goal, because drugs could then be developed to target those genes."
— Abraham A. Palmer, PhD, co-corresponding author

"Seeing the Ces1 signal validate a hypothesis that has been circulating for decades is incredibly exciting."
— Montana Kay Lara, PhD, first author

Implications for Addiction Science

The findings suggest that metabolism of cocaine in the liver may be as important as brain effects in determining addiction risk. Targeting the Ces1 enzyme with medications might reduce the addictive impact of cocaine.

The research team plans to investigate how genetic mutations alter enzyme function and to identify biomarkers from biological samples.

Funding and Contributors

The study was funded by the National Institute on Drug Abuse (NIH) and included multiple coauthors from UC San Diego, The Scripps Research Institute, and Wake Forest University School of Medicine.