Prolonged exposure to cocaine can cause permanent changes in the way genes are switched on and off in the brain, a finding that may lead to more effective treatments for many kinds of addiction, U.S. researchers said.
A study in mice by Ian Maze of Mount Sinai School of Medicine in New York and colleagues found that chronic cocaine addiction kept a specific enzyme from doing its job of shutting off other genes in the pleasure circuits of the brain, making the mice crave the drug even more.
The study helps explain how cocaine use changes the brain, said Dr. Nora Volkow, director of the National Institute on Drug Abuse, part of the National Institutes of Health, which funded the study published in the journal Science.
“This finding is opening up our understanding about how repeated drug use modifies in long-lasting ways the function of neurons,” Volkow said in a telephone interview.
For the study, the team gave one group of young mice repeated doses of cocaine and another group repeated doses of saline, then a single dose of cocaine.
They found that one way cocaine alters the reward circuits in the brain is by repressing gene 9A, which makes an enzyme that plays a critical role in switching genes on and off.
Other studies have found that animals exposed to cocaine for a long period of time undergo dramatic changes in the way certain genes are turned on and off, and they develop a strong preference for cocaine.
This study helps explain how that occurs, Volkow said, and may even lead to new ways of overcoming addiction.
In the study, Maze and colleagues showed these effects could be reversed by increasing the activity of gene 9A.
“When they do that, they completely reverse the effects of chronic cocaine use,” Volkow said.
She said this mechanism is likely not confined to cocaine addiction, and could lead to a new area of addiction research for other drugs, alcohol and even nicotine addition.
“One of the questions we’ve had all along is, after discontinuing a drug, why do you continue to be addicted?
“This is one of the mechanisms that probably is responsible for these long-lasting modifications to the way people who are addicted to drugs perceive the world and react to it,” she said.