Study of gene expression offers hope in search for cocaine treatment

The search for targets for potential cocaine addiction treatments recently took on a new dimension at a Mount Sinai research lab in New York. Researchers led by Eric Nestler, MD, PhD, director of the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai, examined changes in gene expression associated with cocaine use, but did not limit their analysis to genes already known to be associated with addiction.

Their results, published last week in Biological Psychiatry, offer hope for eventually identifying targeted treatments that could have an effect on all reward-related regions in the brain, says one of Nestler's research colleagues. “You could possibly hit one target and affect all of the reward circuitry,” Deena Walker, a postdoctoral fellow in Nestler's lab, tells Addiction Professional.

Walker explains that the study using mice evaluated changes in gene expression throughout the life cycle of addiction. The mice were allowed to self-administer cocaine, and the researchers were able to evaluate differences in gene expression at first exposure, in the period 24 hours after withdrawal, and after a 30-day withdrawal and re-exposure through cues or actual drug use. Many other studies examine brain activity at only one stage of exposure.

Also, Walker explains, the research team examined all six brain regions that make up the brain's reward circuitry. And the researchers looked at a much larger universe of genes than what is typical in these studies.

This led to some noteworthy findings. While some molecular research has tended to identify gene alterations that differ across the brain (perhaps increasing in some areas but decreasing in others), Nestler's team was able to identify molecules that changed in the same direction across different regions. These molecules therefore could be attractive targets for future treatments for cocaine dependence, Walker says.

“Our lab is now focusing on manipulating these molecules,” Walker says.

She adds that because all of the data from this study are publicly available, other researchers in the field mignt be able to use the information to help spur further discoveries in the lab.