Nov. 17, 1997 Scientists at Johns Hopkins have used brain scans to show that intravenous doses of cocaine increase the availability of dopamine, the brain's "feel-good" chemical. Dopamine's activity appeared to increase two to three times over baseline levels in the brain area studied, the putamen, compared to a control area, the cerebellum.
Although the increase cannot yet be directly linked to a cocaine user's "high," investigators report that this is the first time anyone has directly demonstrated that cocaine makes more dopamine available in the human brain.
Improvements in scanning technology eventually may track cocaine's effects on the dopamine-generating nucleus accumbens, a smaller area nearby in the brain that is known to play a role in addictive behavior in animals, adds Godfrey Pearlson, M.D., professor of psychiatry and a lead author on the paper.
"The new finding should advance efforts to understand addiction and treat it by blocking the euphoric effects of drugs," says Pearlson. Brain cells use dopamine by binding the chemical to specific openings on their surfaces. Pearlson used these openings to measure dopamine activity. First, he injected cocaine users with the compound raclopride, which binds to these same receptors. The raclopride was equipped with a mildly radioactive "tag" visible on positron emission tomography (PET) brain scans. Soon after, scientists gave the subjects an injection of a placebo and scanned their brains. Several hours later, the same subjects received a second dose of raclopride followed by a "street-equivalent" dose of cocaine. Then they scanned the patients again. "Because the raclopride and dopamine compete for the right to bind to the same receptors, we could compare the two sets of scans and be virtually certain that the differences in the second group were caused by extra dopamine produced by cocaine exposure," says Thomas Schlaepfer, M.D., now at the University of Bern in Switzerland. "It's likely cocaine affects other neurotransmitters besides dopamine, and these may also be helping create the immediate rush' or feeling of euphoria caused by cocaine," Pearlson explains. "But dopamine is still obviously a very important part of drug addiction. Marijuana, alcohol and heroin all initially act on different brain systems, but the common bond between them is that they all also increase dopamine availability."
The study, published with an accompanying commentary, in the September issue of the American Journal of Psychiatry, was funded by the National Institutes of Health, the Swiss National Science Foundation, the Roche Research Foundation, the CIBA Research Foundation, and other government and private sources.
Other authors were Dean Wong, M.D.; Stefano Marenco, M.D.; and Robert Dannals, Ph.D.
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