Study Finds Cocaine Use Alters Genes in the Brain

DALLAS _ Using cocaine restructures genes in the brain, Dallas scientists have found, a significant step toward understanding how drug use can permanently alter the mind.

“In addiction, the question is not only how people become addicted, but why do they stay addicted? Why do they still crave the drug?” said Dr. Michael Miles, a neuroscientist at Virginia Commonwealth University in Richmond who commented on the new findings. “This is a potential mechanism for that.”

Scientists studying addiction have struggled to learn how drugs leave their mark on users’ brains, even after many drug-free years. Now, researchers at the University of Texas Southwestern hope they are closer to understanding this long-lasting imprint and the development of medications to erase it.

In a study that appeared last week in the journal Neuron, UT Southwestern scientists report that cocaine use can alter genes in brain cells of mice. Some of the changes persist _ and even build _ after cocaine is withdrawn, precisely the type of change that should underlie addiction, said Dr. Eric Nestler, the UT Southwestern neuroscientist who led the study.

The scientists also found that, in experiments that prevented the genetic reprogramming, they could make cocaine less appealing to mice. That opens up new prospects for medicines to thwart addiction, said Nestler, who is chairman of the psychiatry department at UT Southwestern.

In the new study, the UT Southwestern researchers studied genes that contain instructions for a variety of compounds already known to govern both short- and long-term effects of cocaine. Inside cells, these genes _ like all genes _ are wound around special proteins. If the winding is tight, the gene is unusable by the cell. If it’s loose, the gene becomes active.

Nestler and his colleagues discovered that cocaine loosens the proteins around the cocaine-related genes. In one case, this loosening lasted long after the mice stopped using cocaine. This may be part of the imprint that cocaine leaves on the brain when a mouse _ or a person _ becomes addicted, he said.

“The idea (of gene remodeling) has been kicking around for at least 25 years, but no one has been able to show it,” said Jonathan Pollock, chief of the Genetics and Molecular Neurobiology Research Branch at the National Institute on Drug Abuse. The new research may also lead to advances in addiction treatment. Medications that affect the structure of genes are now being tested for Huntington’s disease and certain forms of cancer.

“Now we know to consider those drugs for cocaine addiction, too,” Nestler said.

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