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Missing Clue to Cocaine Addiction Found

Cutting off dopamine and serotonin shuts down the 'high'

WEDNESDAY, May 2 (HealthScout) -- Researchers think they have found the missing clue to cocaine addiction.

For more than 30 years, scientists have thought dopamine, a potent biochemical that can produce euphoria, was the key to how cocaine did its damage. But now researchers say more than dopamine might be at work.

After shutting down the transporters -- signal-sending cells -- for both dopamine and serotonin, another biochemical linked to mood, scientists at the National Institute on Drug Abuse (NIDA) found laboratory mice didn't get the high that makes cocaine so addictive.

They say the discovery, reported in a recent issue of the Proceedings of the National Academy of Sciences, could lead to new treatments.

"It's nice to finally have a coherent picture of this process," says lead study author Dr. George Uhl, chief of the molecular neurobiology branch of NIDA. "Now we know how cocaine is rewarding, so we can do better at this very tricky task of developing anti-cocaine medicines."

Using genetically altered mice, Uhl and his team found that with one dopamine transporter gene and no serotonin transporter gene, the animals still experienced some euphoria after being given cocaine. But that high was completely blunted when both genes were missing.

"It gives new life to this theory" that addiction is controlled by biochemicals, or neurotransmitters, he says.

Researchers at Duke University first threw cold water on the dopamine-addiction theory in 1998 when they found mice without dopamine could still get high from cocaine. But Uhl says it seems the problem is more complicated.

Uhl says ongoing research by his team also points to a third piece in the puzzle of cocaine addiction -- norepinephrine, a biochemical that musters the body's resources in times of stress. However, researchers think norepinephrine causes negative effects, such as the shakes and jitters.

Uhl says the trick with any new treatment will be finding a way to shut down the transport of the biochemicals without affecting their other functions.

One expert in cocaine addiction thinks if the dopamine-serotonin theory holds true in human trials, a combination treatment might do the trick.

"It sounds reasonable to me," says Dr. Tom Kosten, a professor of psychiatry and medicine at Yale University. He says he and other researchers have looked at roughly 700 compounds that might affect dopamine, and they've narrowed that number to three for human trials in the next eight to 10 months. Called tropane analogs, the three compounds are similar to the basic ingredient in cocaine, but do not produce the euphoria of a quick rush of dopamine.

Combining one of the three compounds with an antidepressant which inhibits serotonin could help cocaine users kick the habit, Kosten says.

Larger human trials of such a drug combination might be possible within two to three years, he says.

Statistics on cocaine use show time is of the essence.

Drug Enforcement Administration (DEA) statistics estimate 3.7 million Americans took cocaine, 1.5 million regularly, in 1999. While overall use has not gone up, the number of first-time users increased 63 percent between 1991 and 1998, from 574,000 to 934,000. Cocaine use peaked in 1982, when 10.4 million Americans said they took cocaine.

Over the years, cocaine addiction has been a tough condition to treat. While scientists have touted everything from vaccines and antidepressants to acupuncture, experts say nothing has worked.

What To Do

Uhl says any new treatment for cocaine addiction is still years down the road.

"There isn't a known drug out there that does that. No one expects a single anti-cocaine medicine will solve the problem," he says.

Read more about the 1998 Duke University study on cocaine addiction.

For more on serotonin, visit this site. And to read more about dopamine, go here.

For information on cocaine use in the United States, go to the DEA site.

Check this BBC report on the use of acupuncture for cocaine addiction.

If you or someone you care about has a cocaine problem, check Cocaine Anonymous World Services or these previous HealthScout stories.

SOURCES: Interviews with George Uhl, M.D., chief, molecular neurobiology branch, NIDA, Washington, D.C.; Tom Kosten, M.D., professor, psychiatry and medicine, Yale University, New Haven, Conn.; April 24, 2001, Proceedings of the National Academy of Sciences
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