U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute on Drug Abuse (NIDA) <http://www.nida.nih.gov/>
Embargoed for Release: Thursday, January 7, 2010, 2 p.m. EST
CONTACT: NIDA Press Team, 301-443-6245, <e-mail:media@xxxxxxxxxxxx>
NIDA RESEARCHERS DISCOVER A NEW MECHANISM UNDERLYING COCAINE ADDICTION
Study Offers Promise for Medication Development
Researchers have identified a key epigenetic mechanism in the brain that helps explain cocaine's addictiveness, according to research funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
The study, published in the January issue of the journal Science, shows how cocaine affects an epigenetic process (a process capable of influencing gene expression without changing a gene's sequence) called histone methylation. These epigenetic changes in the brain's pleasure circuits, which are also the first impacted by chronic cocaine exposure, likely contribute to an acquired preference for cocaine.
"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."
Researchers gave one group of young mice repeated doses of cocaine and another group repeated doses of saline with a final dose of cocaine to determine how the effects of chronic cocaine exposure differed from one-time exposure. The study confirms that one of the mechanisms by which cocaine alters the reward pathway is by repressing G9A, a histone demethylating enzyme that plays a critical role in epigenetic control of gene expression.
As previously observed, animals exposed to chronic cocaine displayed dramatic alterations in gene expression as well as a strong preference for cocaine. For the first time, the authors were also able to show that by experimentally reversing the cocaine induced repression of G9a, they could 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.
The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to inform policy and improve practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at www.drugabuse.gov. To order publications in English or Spanish, call NIDA's new DrugPubs research dissemination center at 1-877-NIDA-NIH or 240-645-0228 (TDD) or fax or email requests to 240-645-0227 or <e-mail:drugpubs@xxxxxxxxxxxx>. Online ordering is available at <http://drugpubs.drugabuse.gov>. NIDA's new media guide can be found at <http://drugabuse.gov/mediaguide>.
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <www.nih.gov>.
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