OBSESSED WITH OBSESSIONS

Gamblers, new mothers, over-eaters, and substance abusers. One might say
they're all obsessed, making them a lot like psychiatric researcher Nora
Volkow. Her particular obsession is figuring out why people become
obsessed. "It's a pleasure for me to try to understand things that are not
obvious. It's a drive," says Volkow, now 44, and a year ago, the youngest
person to be appointed associate laboratory director for life sciences at
Long Island's Brookhaven National Laboratory. "It makes me high; there's no
way around it."

Volkow, who was elected to the prestigious Institute of Medicine in
October, can't stop thinking about what lies behind addictions. She relates
the lure of drugs and alcohol to her own life experiences: falling in love,
watching new mothers like her sister think only of the baby, and working
12-hour days, seven days a week, in pursuit of a thrilling idea. She wants
to understand what addictions have in common with such appropriate
obsessions and how the brain chemistry of pleasure can fuel both the good
of love and the evil of drug addiction. The answers could lead to new
pharmaceutical treatments for everything from alcoholism to cigarette
smoking to heroin cravings.

Monkey business. Human and animal behavior has fascinated Volkow since she
was a little girl, growing up in the Mexico City home of her
great-grandfather, exiled Russian revolutionary Leon Trotsky (he was no
longer alive, but she remembers playing with his clothes still in household
closets). As a child, she took in strays, but as a scientist, her love of
animals limited her work. She once stopped an experiment in which a monkey
had to press a lever thousands of times for a minimal amount of drinking
water. "I came in on the weekend and saw this animal was totally
withdrawn," she recalls in her Spanish-accented English. "So I gave him water."

Her eureka moment came while reading an article in Scientific American in
1980. The subject was the new field of neuroimaging-taking pictures of the
living brain. "It sounded like science fiction," she says. But it presented
her with a way to satisfy her curiosity about behavior without
experimenting on animals.

What she found as a researcher at the University of Texas-Houston in 1985
began to put to rest the myth that cocaine was a harmless drug. A world
leader in addiction research, she has studied cocaine's path of euphoria
through the brain by using powerful imaging technology called positron
emission tomography, or PET. "I had images that showed that the brains of
cocaine addicts looked like the brains of stroke patients," she says of her
discovery that the drug interrupts blood flow to the brain. "I showed that
cocaine was toxic to the brain."

Volkow has spent more than a decade exploring the living landscape of
addiction. Her work has led the way in debunking sheer willpower as a cure
by showing that brain chemistry can trigger addictions, which then go on to
further alter brain chemistry. The findings could lead to new drugs that
could identify those most vulnerable to addiction and begin to calm the
cravings of those already caught in its grip.

Right now, Volkow's obsession centers on dopamine, a brain chemical linked
to pleasure and elation. A bite of cheesecake can trigger its release; so
can a baby's smile or an A on an exam. What she's found in sorting out the
red, yellow, and blue blotches on brain images is that addicts have fewer
available dopamine receptors than do normal people. Long-term alcoholics
have even fewer receptors. The receptors transmit dopamine signals to the
reward circuits in the brain; the lower the number of receptors, the weaker
the signals-and the less joie de vivre. A common thread among drugs of
abuse, including alcohol, cocaine, heroin, marijuana, and nicotine, is
their ability to elevate dopamine levels.

Prone to snort. One brain chemical alone cannot create an addict. But when
a brain that is unable to produce adequate dopamine collides with a
stressful environment, and then is presented with opportunities to drink,
snort, smoke, or shoot up, the result can be addiction. "There is an
addictive personality," insists Volkow.

The addict's brain may be doubly jinxed. Fewer receptors not only make
people more vulnerable to addiction but also may prevent them from feeling
normal pleasures-like love or a sunset.

Volkow knows the lure of such joys and can empathize with those who need
chemicals to make it happen. "I get excited by ideas. I am addicted to
Bach. I get addicted to writers. Now I'm reading [Japanese novelist] Haruki
Murakami. I know I will read everything by him," she says. She speaks
quickly, as though her mind is crackling with the next idea before the
words describing the last idea are fully out.

Volkow is now looking at an area of the brain, the frontal cortex,
associated with higher thinking. Few had deemed it a culprit in addiction.
PET images of that area showed similar activity in both addicts and people
with obsessive/compulsive disorder.

"It hit me completely," she says. "These two diseases both have
obsessive/compulsive behavior in common. One is an uncontrollable urge to
take drugs, the other a compulsion about rituals." And that would take the
brainscape of addiction one step further. Addiction may not simply be a
search for pleasure. Drugs could change brain chemistry in ways that
trigger a compulsion to take more drugs, long after the early stage of
quick pleasure wears off. "Drugs feel good, but that's the trivial
explanation. What is the role of brain dopamine in the loss of control?"
she asks. One can only imagine the pleasure-releasing surge of dopamine
through the synapses of her brain as she sparkles with another idea.

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