New Cocaine-Addiction Mechanism Revealed

Experts at the National Institutes of Health's (NIH) National Institute on Drug Abuse (NIDA) announce that they recently determined a new mechanism underlying severe cocaine addiction. The key epigenetic mechanism works inside the human brain, promoting cocaine's addictiveness, and making it one of the most dangerous drugs on the planet. Details of the investigation appear in the January issue of the top journal Science. NIDA is a component of the Department of Health and Human Services.

“This fundamental discovery advances our understanding of how cocaine addiction works. Although more research will be required, these findings have identified a key new player in the molecular cascade triggered by repeated cocaine exposure, and thus a potential novel target for the development of addiction medications,” Dr. Nora D. Volkow, the director of NIDA, reveals. She adds that the recently discovered process has the ability to alter and otherwise influence gene expression, only without actually changing that certain gene's sequence. The process involved in cocaine addiction is called histone methylation.

According to NIDA researchers, epigenetic changes also take place inside the brain's pleasure circuitry. This is among the first parts of the human brain to be targeted by compounds released during cocaine consumption. The drug directly alters the pleasure and reward neural pathways, by inhibiting the action of a histone demethylating enzyme called G9A. The small molecule is of paramount importance in the epigenetic control of gene expression. The research was conducted on two groups of unsuspecting lab mice, one of which was fed multiple doses of cocaine, while the other was given saline, and then a single dose of the drug. The aim was to investigate the differences between the two groups.

“The more complete picture that we have today of the genetic and epigenetic processes triggered by chronic cocaine give us a better understanding of the broader principles governing biochemical regulation in the brain which will help us identify not only additional pathways involved but potentially new therapeutic approaches,” expert Dr. Eric J. Nestler says. He has been a study investigator, and is also the director of the Mount Sinai School of Medicine Brain Institute. Funding for the new research came from the DHHS, NIH and NIDA.