91ÊÓƵ

1 Jan 2001

By Susan Brink

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 "I came in on the weekend and saw this animal was totally withdrawn," she recalls in her Spanish-accented English.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.

WORTH WATCHING:

"A charge to stop depression"

A tiny jolt of electricity to the brain could one day effectively treat depression. That's the dream of psychiatrist John Rush of Dallas's Southwestern Medical Center.

Rush's vision was born in a hospital labor room in the mid-1970s. Neurophysiologist Jake Zabara was massaging his pregnant wife's vagus nerves, on the right and left side of the neck. That calmed her and eased her pain. Zabara reasoned that the massage altered brain waves--also a way to stop seizures. To experiment on epileptics, he invented an implant the size of a thin pocket watch. Placed under the left armpit, the VNS (vagus nerve stimulation) device emits an electrical charge about every five minutes. The device stopped seizures in dogs; in 1988, the first VNS was implanted in a human with epilepsy.

Scientists noticed that VNS improved the mood of epileptics, so Rush has taken the torch of innovation from seizures to depression. He explains that the vagus nerve routes signals through the brain's nucleus to centers controlling emotion, motivation, and appetite. "By stimulating [the nerve], maybe you can change its communication," says Rush. A pilot study last year tested the device on 30 chronically depressed patients unaffected by antidepressants. Four out of 10 showed an improvement in mood.

A controlled clinical trial of 4,500 could be the clincher. All patients will receive implants, but half will be activated for 10 weeks while the other half remain dormant. The second half will then have their devices activated. Results should be known in 2003.

Copyright 91ÊÓƵ 2001 U.S.News & World Report, L.P. Reprinted with permission.