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Hard to kick. Human and rat cocaine users respond to signs of drug use even after long periods of abstinence.

Probing the Riddle of Relapse

Even after drug addicts beat their habits, they face a daunting challenge: simply returning to the place where they took drugs can trigger irresistible cravings that may lead to relapse. Now neurobiologists have shown that lab rats respond in the same way, even after months of abstinence, making those animals a potentially valuable tool for finding ways to help former addicts stay clean.

It was already clear that rats and humans respond to cocaine in similar ways: Both get a boost of energy from the drug, develop tolerance for it, and show signs of addiction. Cocaine appears to boost levels of the neurotransmitter dopamine in the brain in both species, and both will actively seek the drug. For rats, that usually means pressing a lever to get an injection of cocaine.

To see whether rats and people also share similarities when they relapse, a group led by Friedbert Weiss at the Scripps Research Institute in La Jolla, California, taught rats to associate a squirt of cocaine with a tone. Then the researchers withdrew the cocaine and stopped playing the tone. Four months later, the researchers played the tone again. Much like Pavlov's dogs, the rats immediately started pressing a cocaine-delivering lever in response, the researchers report in the 13 February issue of the Proceedings of the National Academy of Sciences.

The similarity between rats and humans appears to be brain-deep. Dopamine-rich regions in the brains of the "relapsed" rats showed chemical signs of increased neural firing. In imaging studies in humans, similar brain regions are turned on when people are suffering from cocaine craving. Furthermore, a drug that muffles cocaine's effects in humans prevented the rats from relapsing.

The identification of what happens in a rat's brain when it falls off the wagon "gives us a target against which we can work to find appropriate medications to deal with relapse," says Alan Leshner, director of the National Institute on Drug Abuse in Bethesda, Maryland.

Related sites

The paper's abstract is available online

National Institute on Drug Abuse