With hope of one day curing humanity of cocaine addiction, medical investigators at Mount Sinai Hospital in New York say they’ve discovered more about how the drug alters the brain’s reward circuits.
Research physician Eric J. Nestler says he and his colleagues found in a study of laboratory mice that chronic cocaine exposure led to elevated levels of the PARP-1 enzyme, which along with a synaptic gene affected how genes are expressed in the nucleus accumbens. Prolonged cocaine use changes the brain not by altering DNA but by expressing, or repressing, specific genes that are encoding synaptic proteins within the genetic information. The same protein found critical to cocaine addiction has been under investigation by other scientists developing cancer treatments. “This discovery provides new leads for the development of anti-addiction medications,” Nestler said in a statement.
After discovering the protein’s epigenetic effect on cocaine addiction, the investigators used a technique known as chromatin immunoprecipitation sequencing to identify exactly which genes are altered by the protein. They focused on a target gene known as Sidekick-1, a cell adhesion molecule highly concentrated at brain synapses that direct such intercellular connections. By using viral gene mediation, the team was able to overexpress the Sidekick-1 gene, finding major changes to the brain’s pleasure center. Not only did a greater role for Sidekick-1 increase satisfaction with cocaine stimuli but the actual structure of the brain and it’s connections changed, too.
Kimberly Scobie, a postdoctoral fellow working on the study, touted the study’s findings as important to cocaine addiction research. “It is striking that changing the level of PARP-1 alone is sufficient to influence the rewarding effects of cocaine,” she said. The study suggests a new direction for therapies treating cocaine addiction in the United States, with 1.4 million of our countrymen dependent on the drug, according to the U.S. National Institute of Drug Abuse.