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Researchers Gain Insight on Blocking Cocaine 'High'
May 1, 2001

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Research Summary

Researchers have determined how to block the pleasurable effects of cocaine in mice, thus setting a course for medications to treat cocaine addiction in humans, Reuters reported April 26.

"We now know how cocaine produces its euphoria, something that previous studies have not been able to identify correctly," said Dr. George Uhl of the National Institute on Drug Abuse, who led the study.

To determine how cocaine causes euphoria, researchers blocked certain types of "transporters" in the brain of genetically engineered rats. According to Uhl, transporters limit the cells' exposure to chemical messengers, and, consequently, limit the neurotransmitters' effects. Cocaine has been found to block transporters for the neurotransmitters dopamine, serotonin and norepinephrine, thus increasing the brain's exposure to these chemicals.

In the study, mice that had no dopamine transporters appeared to become addicted to the cocaine. The same thing happened in mice that lacked serotonin transporters. But when the mice lacked dopamine transporters and at least 50 percent or more of the serotonin transporters, they did not choose the cage where cocaine was available.

"Many brain processes have redundancy, so that they can continue even if part of the brain is damaged or blocked by drugs. Cocaine may be so rewarding because it works on two circuits that both can provide drug reward signals," Uhl explained.

"These findings are important for treatment since no effective cocaine treatment now exists," he added. "Many of the attempts at cocaine treatments to date have focused on the dopamine transporter alone. We now know that this is not enough. Effective treatments are likely to have to influence both the dopamine and serotonin reward circuits in the brain in order to be effective. Making drugs that could do this is feasible, but a bit tricky."

The study's findings are published in the April 24th issue of the Proceedings of the National Academy of Sciences.

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