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.