Originally created 05/14/98

Studies: Serotonin has big role in cocaine addiction



LOS ANGELES -- The chemical messenger serotonin is turning out to be a bigger player in cocaine addiction than previously thought, according to two studies that could help researchers find new approaches to treating and preventing drug abuse.

The studies released Wednesday looked at the roles of dopamine and serotonin in laboratory mice that were forced to press levers to get doses of cocaine.

Researchers have long held that increases of dopamine -- a chemical associated with movement, thought, motivation and pleasure -- in the brain produce some of the euphoria and addictive effects of cocaine.

Serotonin -- involved in emotions, mood, and probably sleep and aggression -- was thought to play some role in achieving a high. But the new studies show it also plays an important role in how vulnerable an animal, or human, may be.

"We used to have a religion called the dopamine religion that said that you could explain anything solely on the basis of dopamine," said Alan I. Leshner, director of the National Institute on Drug Abuse.

The new results suggest more attention must be paid to serotonin, he said. "That opens a new line of thinking because we know serotonin is important in many other mood states, like depression."

Work was funded by Leshner's institute and led by Rene Hen at Columbia University and Beatriz Rocha at the University of North Texas.

They found that specially bred mice lacking a gene involved in the brain's response to serotonin were more motivated to take cocaine than normal mice. They were also more sensitive to the drug's effects.

The mutant mice also showed an increased attraction to alcohol and more impulsiveness, a trait often associated with drug abuse.

That study, underscoring the role of genetics in addiction, appears in Thursday's issue of the journal Nature.

In the other study, which will appear in the June issue of the journal Nature Neuroscience, Marc G. Caron found evidence that cocaine's effects are not solely controlled by the dopamine system.

Caron has been working with the brain cell circuits in which one brain cell signals another by releasing bits of dopamine. Then the first cell retrieves the dopamine with a structure called a dopamine transporter.

Researchers had believed that cocaine works by attaching itself to the transporter so it can't retrieve the dopamine. That allowed more dopamine to circulate around the cell, providing the high.

Caron's team, which also includes Ms. Rocha, thought that giving cocaine to a specially bred mouse without a dopamine transporter would take away the cocaine target and eliminate the mouse's normal desire for the cocaine.

Scientists were surprised to find mice without the transporter still pressed the lever to get more of the cocaine. Serotonin or some other mechanism may initiate and maintain the attraction to cocaine, said Caron, a Howard Hughes Medical Institute investigator and professor of cell biology at Duke University Medical Center in Durham, N.C.