Yale Bulletin and Calendar

September 20-27, 1999

Volume 28, Number 5

Study shows affect of long-term abuse of cocaine lingers in brain even after years of abstinence

A Yale research team has found that repeated use of cocaine causes changes in the brain that persist long after the drug is no longer used.

"There have been no adequately effective treatments for cocaine addiction because we know very little about changes in the brain that are responsible for addiction," says Eric Nestler, professor of psychiatry and neurobiology. "Our new findings help us understand addiction, so that eventually we can better treat it."

The findings published in the Sept. 16 issue of Nature magazine were based on a three-year study conducted by Nestler's team and researchers at two other universities. They found that long-term use of cocaine triggers the production of a new gene, called FosB. This gene acts as a sustained molecular switch to increase sensitivity to cocaine.

Earlier studies, says Nestler, showed chronic exposure to other drugs of abuse, such as amphetamines, morphine, nicotine, and PCP, produces the same neurobiological changes.

"A cocaine addict is addicted because of many changes the drug produces in the brain," he says. "Some of these changes persist even after years of abstinence."

The researchers demonstrated the importance of FosB as one of these long-lasting changes by using an animal model. They observed a dramatic increase in the animal's responsiveness to cocaine when the FosB gene was turned on specifically in brain regions important for the formation of addiction. The researchers also identified a target gene through which FosB produces these behavioral effects.

These changes triggered by FosB are unique in that they occur only with chronic cocaine use and are not seen with minimal use, says Nestler. Also, once formed, the changes persist in the brain for a long period of time, he adds.

"Although this is just one of the many changes that likely contribute to addiction, production of FosB clearly provides a mechanism by which drug exposure can cause relatively long-lasting changes in the brain," he says.

Nestler says it may one day be possible to neutralize these more persistent neurobiological changes and reduce the likelihood of continued drug addiction.

-- By Jacqueline Weaver

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