MAPPING COCAINE'S IMPACT

MRI machine yields clear images of drug's effect on brain

All that could be seen of the drug addict were his gray wool socks sticking
out of an MRI machine the size of a walk-in closet.

He'd been in there about an hour when a technician pushed a big white
button and infused 40 milligrams of cocaine into his bloodstream.

Two psychiatrists watched intently, along with a heart specialist, drug
counselor and nurse. If all went well, they would capture amazingly clear
pictures of the drug's effects on this man's brain, a step toward mapping
addiction's grip and, ultimately, perhaps curing it.

But at this moment the team focused on only getting through the next
half-hour without a mistake.

For 90 seconds, nothing happened. Then the man's heart picked up speed.
Ninety beats a minute, then 130, 135. His blood pressure zoomed to 194 over
116. A number came up on a computer screen: Rush 4.

``He's getting maximal rush,'' psychiatrist Hans Breiter said.

The man inside the MRI machine had just signaled how much he liked it.

A scale of one to four was being used to rate his euphoria, and four meant
really good.

It was a rush in the interest of science. In this unusual experiment at
Massachusetts General Hospital, scientists were literally looking inside a
man's head to see what cocaine does. Their MRI, or magnetic resonance
imaging machine, programmed to run far faster than conventional models,
rattled off one brain image a second.

It was quickly over. Within a couple of minutes, the rush fell to two, then
one. Then came less pleasant feelings. Low two, the man reported. Low
three. It meant he felt jittery, out of sorts.

Finally, the numbers began to rise on another scale, his hunger for more.
Craving three.

After promising not to go looking for cocaine that night, the addict was
sent home with a lecture on the drug's dangers, an offer of rehab and a
supermarket credit for $260.

Volunteer No. 34 received what for him was a moderate amount of cocaine and
left behind 200 images of what it did to his brain.

Changing the Brain

The U.S. National Institute on Drug Abuse is paying for this and similar
experiments in the hope that understanding cocaine's effects will lead to
medicines to blunt them.

How does cocaine change the brain? What's out of whack 10 minutes after
snorting it? A month after? A year? Until recently, answers could be
surmised only from animal experiments. Cocaine is perhaps the most
addictive substance known. A rat will ignore food, water and sex and take
cocaine until it dies, but a rat cannot say how it feels. Now the fast
MRIs, and companion technology, offer a window inside the human head.

About two weeks after the experiment on addict No. 34, Breiter called up
his brain scans.

``Tons of areas are lit,'' he said, pointing to a scattering of purple and
yellow blotches. ``But it's not at all a global response. It's very
specific.''

Each bit of colour showed the intensity of work done by different parts of
the brain under cocaine's influence. MRI does this by measuring the oxygen
content in blood. Because the body needs more oxygen when busy, blood
oxygen levels reveal which parts of the brain are most active.

The snapshots reveal that cocaine activates the mesolimbic dopamine system,
a strip of nerve cells running from deep in the brain's centre to its outer
fringes - the chemical pipeline linking the body's pleasure centre that
makes you feel good when you bite into a perfect steak or find a $10 bill
on the street.

Researchers found 90 parts of the brain turned on during cocaine's rush.
But as euphoria ebbs and craving sets in, almost all fade out, leaving only
a few structures - especially the amygdala and the nucleus accumbens -
still working hard.

Keeps Addicts Hooked

This was surprising. The amygdala and nucleus accumbens are part of the
system that gives pleasure. So why is this system involved in craving,
which is the motivation to get more pleasure?

Making sense of craving is a hot research area, because craving keeps
addicts hooked.

Cocaine, nicotine, alcohol, heroin and most other drugs of abuse exploit
the same system that rewards us for eating, drinking and having sex -
maintaining the species.

The drugs increase the supply of dopamine, a protein that triggers the
body's pleasure circuits. Cocaine's trick is to block dopamine recycling,
so it's not flushed out of the system as usual, but spikes to astronomical
levels. Overloaded with dopamine, the brain cuts production. The addict
makes up the shortfall by snorting more cocaine.

Two years were devoted to designing the experiment to minimize risks,
recruiting only heavy, chronic cocaine users, who are urged to quit the
habit even before the experiment begins.

``Frankly, even I still have my doubts about whether this is OK,'' said Dr.
Steven Hyman, who set up the experiment before turning it over to Breiter.
``But we will learn things we could never possibly learn from animals.

``A rat in a cage with an IV is not the same as an addicted human.''