Studies shed light on cocaine's kick

By Maggie Fox

LONDON (Reuter) U.S. researchers said Wednesday they had demonstrated how
cocaine gets people ``high'' and predicted their tests could help develop
better drugs to treat addicts.

Tests on mice have shown that cocaine acts on dopamine, a neurotransmitter
that carries signals between brain cells and is important to movement and
motivation.

Higher levels of dopamine create feelings of euphoria.

In mice, cocaine blocks the reuptake of dopamine keeping it from being
absorbed back into cells and thus keeping more of it around for longer.

Nora Volkow of Brookhaven National Laboratory in New York and colleagues
found this also happens with people.

Positron emission tomography (PET) scans showed doses of cocaine blocked
between 60 percent and 77 percent of the enzyme that is responsible for
reuptake of dopamine.

``This is the first demonstration in humans that the doses used by cocaine
abusers lead to a significant blockade of dopamine transporter, and that this
blockade is associated with the subjective effects of cocaine,'' they wrote
in a letter to the science journal Nature.

The dopamine transporter enzyme would be a good target for an anticocaine
drug, but they said any such drug would have to be given at high enough doses
to completely block the enzyme.

Volkow's group recruited 17 cocaine users, injected them with cocaine and
used the PET scans to see what was happening in the brain. The volunteers
were asked to describe whether they felt ``high, a ``rush,'' ``restlessness''
or ``cocaine craving.''

Cocaine acts very quickly, which could be why it is such a popular drug, they
said.

But they also showed that cocaine's kick wears off quickly. ``After peak
effects, selfreports for the high declined faster than the rate of clearance
of cocaine from the brain,'' they wrote.

Dopamine's role was now well known, they said. ``But addiction to cocaine
involves other effects, such as craving, loss of control, and compulsive
intake; the role of the dopamine system in these effects is less well
understood.''

So they used PET scans to watch what happened when 20 cocaine addicts and 23
nonaddicted volunteers took methylphenidate, a drug that acts like cocaine.

The addicts did not get as ``high'' as the nonusers, and also said
methylphenidate gave them cocaine cravings.

Addicts had an extra response to the drug in the thalamus, which relays
sensory input to the cerebral cortex, the area of the brain that controls
movement, sense, thought and memory. Nonaddicts did not show this response.

Volkow's group said their findings could lead to better understanding of how
cocaine acts in the brain.

Scientists are looking for a way to help cocaine addicts quit. In 1995 a team
at the Scripps Research Institute in La Jolla, Calif., said they had created
an anticocaine vaccine using a chemical very similar to cocaine, known as a
conjugate, to create antibodies against the drug.