Researchers Understanding Cocaine Addiction Better

How the drug influences gene expression in the brain's pleasure circuitry without changing the gene's sequence is explained in a NIDA-funded study. The knowledge may lead to more effective treatment medications.

Researchers working with funding from the National Institute on Drug Abuse have published a paper explaining how cocaine influences gene expression in the brain’s pleasure circuitry without changing the gene’s sequence. This understanding may lead to more effective treatment medications.

The study is published in the January issue of the journal Science. It details cocaine’s effect on an epigenetic process (a process capable of influencing gene expression without changing the genetic sequence) called histone methylation. The epigenetic changes in the brain's pleasure circuits probably contribute to an acquired preference for cocaine, according to NIDA’s release about the results.

"This fundamental discovery advances our understanding of how cocaine addiction works," said NIDA Director Dr. Nora D. Volkow. "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."

The research gave repeated doses of cocaine to a group of young mice but saline doses with a final dose of cocaine to a second group to determine how the effects of chronic cocaine exposure differed from one-time exposure. The study confirmed cocaine “alters the reward pathway by repressing G9A, a histone demethylating enzyme that plays a critical role in epigenetic control of gene expression,” according to NIDA. The authors experimentally reversed the cocaine-induced repression of G9a and were able to block the changes in gene expression and inhibit the enhanced preference for cocaine.

"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," said Dr. Eric J. Nestler, study investigator and director of the Brain Institute at Mount Sinai School of Medicine.

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