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Epigenetic changes may explain cocaine addiction

Kathleen Blanchard's picture

Researchers now understand how cocaine addiction occurs. Scientists have discovered that cocaine use leads to epigenetic changes from repeated exposure to the drug; linked to an enzyme that alters the reward pathway in the brain.

The findings that cocaine addiction is linked to changes in gene expression could lead to new therapies to help individuals battling drug addiction. Changes in the circuitry of the brain that controls pleasure and occur over time affects epigenetic changes. The process does not change DNA sequencing, but rather the way genes behave. By studying mice, the researchers found that cocaine exposure that leads to addiction alters the reward pathway in the brain by repressing G9A, a histone demethylating enzyme that plays a critical role in epigenetic control and the way genes are expressed.

"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."

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The findings that cocaine alters genes and the pleasure circuitry of the brain and causes addictiveness comes from comparing two groups of mice - one group of young mice was repeatedly given cocaine, and another group repeated doses of saline, followed by a dose of cocaine. The researchers confirmed that chronic cocaine exposure alters the reward pathway by repressing the G9A enzyme.

"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.

Cocaine and other drug addictions are linked to the brain and to behavior. Until now few clues have been available as to why some individuals develop drug addiction and others do not. A lack of understanding by scientists of how cocaine leads to addiction has been a limiting factor for successful treatment of the disorder. Drug abuse and mental disorders frequently occur together, making the new study important.

Scientists now know that cocaine alters the expression of genes through its effect on epigenetics. Cocaine addiction, shown by the mouse studies, suppresses the G9A enzyme which is responsible for how genes behave, altering the pleasure pathway in the brain.