BRAIN SCANS PROVE DOPAMINE'S INVOLVEMENT IN COCAINE ABUSE

Scientists at Johns Hopkins have used brain scans to show that
intravenous doses of cocaine increase the availability of dopamine, the
brain's "feelgood" 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 dopaminegenerating 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 "streetequivalent" 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.

JHMI