Study Hints at Gene Therapy for Addiction

Researchers successfully reduced the rewarding effects of cocaine by blocking the activity of certain genes in the nucleus accumbens portion of the brain, according to the National Institute on Drug Abuse (NIDA).

Using molecular analysis, researcher Eric Nestler, M.D., Ph.D., of the Mount Sinai School of Medicine and colleagues studied changes in gene activity in lab mice that were administered cocaine. Using genetic markers, the researchers were able to map the genetic impact of chronic cocaine use in the nucleus accumbens, a part of the brain heavily involved in reward.

“This analysis provides fundamentally new information about the range of genes that are altered by cocaine in this brain region,” said Nestler. “For example, this study demonstrated, for the first time, that a family of genes called the sirtuins are activated in the nucleus accumbens by chronic cocaine administration and contribute to addiction-related behaviors in animal models. We showed that blocking the activity of the sirtuins specifically in the nucleus accumbens reduced both cocaine’s rewarding effects and the motivation to self-administer the drug.”

Nestler said that the study showed that sirtuin inhibitors could be used to treat cocaine addiction.

“This study’s findings enable us to glimpse for the first time exactly how cocaine modifies the activity of genes in regions of the brain that mediate reward,” said NIDA Director Nora Volkow. “In addition, this research has identified a novel family of genes that appear to play a key role in the brain’s response to cocaine. These genes represent promising new targets for the development of medications to treat cocaine addiction.”

The study was published in the May 14, 2009 issue of the journal Neuron.