Genetic Study Points to Liver Enzyme in Cocaine Addiction Risk
"The metabolism of cocaine in the liver may be as relevant to addiction risk as brain-based genes."
A study published in Nature Communications has identified genetic markers associated with compulsive cocaine use in rats. Researchers from the University of California San Diego, along with colleagues from The Scripps Research Institute and Wake Forest University School of Medicine, analyzed nearly 900 genetically diverse rats to map genetic regions linked to addiction-like behaviors.
Key Findings
The study identified six major genetic regions related to the escalation of cocaine intake and the time between doses.
One of these regions, known as Trak2, had been previously associated with addiction in humans, supporting cross-species relevance.
Another key finding was the Ces1 genetic region, which directs the production of a liver enzyme that breaks down cocaine. Variations in the Ces1 genes were associated with the frequency and compulsivity of cocaine self-administration.
Methodology
The research team used heterogeneous stock rats, a population designed to mimic human genetic diversity. Behavioral studies measured the frequency and compulsivity of the rats' self-administration of cocaine. Genetic analysis involved examining millions of markers per animal to map the identified behaviors to specific genetic regions.
Implications
The authors stated that the results need confirmation in humans, but that the Ces1 enzyme presents a potential target for developing medications to 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
The study was funded by the National Institute on Drug Abuse, part of the National Institutes of Health.