Mar. 4, 1999 CHAPEL HILL - Dopamine, a chemical messenger believed for more than two decades to be the end point of the brain's pleasure system, appears not to be that molecular reward after all, a new study shows.
The University of North Carolina at Chapel Hill study suggests instead that dopamine plays an early central role in pleasure, but another chemical -- possibly serotonin -- actually rings the chimes for humans and animals alike.
Researchers say their discovery should become important in the search for solutions to substance abuse and addiction problems, researchers say.
A report on the findings appears in the March 4 issue of the journal Nature. Authors are Drs. Paul A. Garris, a postdoctoral fellow at UNC-CH now at Illinois State University, and R. Mark Wightman, William Rand Kenan Jr. professor of chemistry at UNC-CH. Others are Michaux Kilpatrick, an M.D.-Ph.D. student in Wightman's laboratory; Dr. Melissa A. Bunin, a former graduate student doing postdoctoral work in Australia; graduate student Daren Michael, and Dr. David Walker, now a Duke University postdoctoral scientist.
In what the journal dubbed "something of a technical tour de force," the studies first involved developing a carbon fiber electrode one tenth the thickness of a human hair and coating it with glass.
"When implanted in rat brains, this micro-sensor allows us for the first time to measure very small amounts of chemical messengers, or neurotransmitters, on a split-second time scale," Wightman said. "That was not possible before."
Using their device coupled with electronic equipment, Wightman and his students can record what happens inside the brain as neurotransmitters such as dopamine interact with one another in real time. They incorporated into the work experiments pioneered by Canadian researchers in which rats quickly learn that by pressing a lever, they can receive a tiny but pleasurable shock to their brain through deep probes implanted there.
"We discovered that when we applied the electric shock to untrained rats, we clearly saw dopamine, but when the animals themselves applied the shock, little or no dopamine appeared," Wightman said. "Considering that scientists have been pretty satisfied that dopamine was the important thing, this was a big surprise."
Dopamine may be involved in learning or anticipation of reward, he said. It clearly is not responsible for continuous pleasure, however, or the chemists would have detected a lot of it when trained rats repeatedly pressed the lever, too.
The new work promises better explanations of how such abused chemicals as nicotine, alcohol, cocaine and amphetamines act in the brain, Wightman said. It also might help identify less toxic substances that could ease withdrawal and make it more successful.
"Because nobody ever had a way of making these kinds of measurements, we think this is really a big jump ahead," he said. "Often it is new technology that in fact drives new findings in science and medicine."
The National Institute of Drug Abuse and the National Institute of Neurological Disorders and Stroke supported the continuing studies. A feature on the work in Wightman's laboratory will appear in April in "Endeavors," UNC-CH's research magazine.
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