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Common Gene Links Learning and Addiction

Mouse study gives researchers new target for treatment

THURSDAY, Feb. 19, 2004 (HealthDayNews) -- A gene that affects learning may also play a role in developing a drug addiction.

That's the conclusion of a new study appearing in the Feb. 19 issue of Neuron.

In tests on mice, researchers from the Howard Hughes Medical Institute at Duke University Medical Center found six genes that change in response to repeated drug exposure, including one, called post-synaptic density-95 (PSD-95), that other researchers have shown is involved in learning.

"We found several genes that might be involved after animals are exposed chronically to drugs," says study co-author Marc Caron, an investigator from the department of cell biology at Howard Hughes Medical Institute. "One of these genes has been previously implicated in the process of learning in animals."

These findings could eventually lead to research to find ways to assess an individual's level of susceptibility to drug addiction. But both Caron and his co-author, Howard Hughes Medical Institute fellow Wei-Dong Yao, say applying their findings to humans would be a big leap.

"How humans get hooked on drugs is a very complex process, and there are probably many genes involved," Caron explains. "This gene may be one of many genes involved in the changes that occur in the brain that lead to addiction."

"We know this molecule is involved in the process of addiction," says Yao, who adds this information gives researchers a new target to try to develop a therapy that would interfere with this process.

For this study, Yao, Caron and their colleagues looked at how 36,000 different genes in mice responded after exposure to cocaine and then compared them to normal mice. They studied a particular area of the brain called the striatum because previous research has shown that exposure to cocaine causes a dramatic increase in communication between nerve cells in this part of the brain.

The striatum, a reward center in the brain, produces the feelings of pleasure that typically keep drug users craving more and more of a drug.

Caron says the mice they tested were not addicted to drugs but instead were in the initial stages of addiction, where they had developed a "hyper-responsiveness" to drugs.

The researchers found six genes with either increased or decreased activity in response to cocaine exposure. The role of three of the genes is unknown, according to the researchers. Two genes had previously been implicated in the development of addiction, and one -- PSD-95 -- had been associated with learning but never before with addiction.

Earlier studies found mice with low levels of PSD-95 take longer to learn new tasks. In the current study, the Duke researchers found that PSD-95 levels dropped by about 50 percent in the drug-exposed mice.

The researchers believe PSD-95 probably is involved in addiction to other drugs -- such as nicotine, alcohol, morphine and heroin -- that have similar effects on the brain.

Of particular concern, Caron says, is that the changes in PSD-95 remained the same even two months after drug exposure. "These changes were very long-lived and seem very hard to reverse, and are almost permanent," he says.

And that, he says, may be one of the reasons it's so hard for people addicted to drugs to quit.

More information

To learn more about preventing drug and alcohol abuse, visit the University of Toronto's Centre for Addiction and Mental Health. For more information on addiction treatment, go to the National Institute on Drug Abuse.

SOURCES: Marc Caron, Ph.D., Howard Hughes Medical Institute Investigator, Duke University Medical Center, Durham, N.C.; Wei-Dong Yao, Ph.D., Howard Hughes Medical Institute fellow, Duke University Medical Center, Durham, N.C.; Feb. 19, 2004 Neuron
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