Cocaine's Lock On Users Goes Beyond Feeling Good

Science & medicine

April 15, 1990|By William Booth Washington Post

No one knows exactly what a squirrel monkey feels when it imbibes cocaine. But government scientists at the Addiction Research Center in Baltimore know this: A monkey will flip a switch for hours just to get another dose of cocaine. And just as some humans will go on a reckless binge of abuse, so too will a monkey hit the switch for more and more cocaine until researchers stop the experiment.

But scientists caution that just because they can get a monkey to feed its addiction so voraciously, it does not necessarily support the popular belief that cocaine is the most addictive of abused drugs.

How drug produces a high

Indeed, they say, the reason the animal keeps hitting the lever may just be because cocaine makes the monkey super-alert and hyperactive.

A monkey might be just as addicted to alcohol, but after a few drinks, in contrast to cocaine's effect, the monkey might stop hitting the lever because it feels sleepy or dazed.

In the last few years, drug researchers have learned an enormous amount about cocaine. Not only do they know more about its true addictive properties, they now at last have a rough idea of how cocaine produces its high.

Addiction scientists have learned, for example, that the drug stimulates a still-mysterious pathway in the brain that is involved in feelings of pleasure and reward.

Indeed, some scientists think they now know at least one region of the brain where cocaine does its work, a structure called the nucleus accumbens, which is responsible for helping humans orient and move toward things they find pleasurable, whether the object of their desire is a member of the opposite sex, a fine wine or a rock of crack cocaine.

In addition, researchers know the exact molecular site in the nucleus accumbens where the cocaine molecule binds to its special receptor. This in turn has led to a better understanding of how cocaine acts to overstimulate certain nerve cells in the brain, a phenomenon that makes users feel good.

Armed with this knowledge, new drugs are being developed to treat the worst symptoms of withdrawal, to suppress co-caine craving and to reduce cocaine-associated depression.

The drug pipeline

When a user smokes crack in a pipe, researchers believe he is employing one of the most efficient drug delivery systems known.

In both animals and humans, scientists say, smoked cocaine reaches the brain so quickly that it is almost impossible to distinguish a dose delivered by intravenous injection from a dose delivered by a glass pipe.

''How fast does it get to the brain? We're not sure. It's too fast to measure in the lab,'' said Jonathan Katz, a behavioral pharmacologist at the Addiction Research Center, a branch of the National Institute on Drug Abuse. Katz said he assumes crack cocaine reaches the brain in seconds.

Unlike snorting cocaine powder, a relatively slow and inefficient route, smoking crack delivers the drug directly to the lungs, where it is readily absorbed by the blood, pumped once through the heart and then up to the brain.

One researcher compared smoking crack to driving a nail of cocaine directly into one's forehead.

A ''single significant dose'' of cocaine - in other words, enough to get a person with a history of cocaine use high - increases breathing, boosts blood pressure and may double heart rate. Hunger, fatigue and depression fade. A subject feels vigorous, happy, hypersexual, friendly and alert. Some scientists describe this collection of sensations as euphoria.

While a full explanation of how cocaine produces euphoria remains elusive, re-searchers do know that the drug appears to affect the limbic system, the part of the brain involved in the powerful emotional responses, of which the best-known are those important to human survival, such as the primal urges to feed, fight, flee and reproduce.

While several components of the limbic system are under study, the one area that appears to get the most action is the nucleus accumbens. The nucleus accumbens is uniquely situated to communicate between the limbic system and the part of the brain called the motor cortex, which directs movement.

''When you see a pretty girl and are alert to her presence and orient toward her, or when you smell a good bordeaux wine sauce and move toward the smell, it is the nucleus accumbens that is helping you orient and move toward those things you perceive as pleasurable,'' said George Koob, a psychopharmacologist at the Research Institute of the Scripps Clinic in San Diego.

The lure of cocaine

Scientists believe that cocaine stimulates the nucleus accumbens by meddling with a special chemical messenger called dopamine.

In the nucleus accumbens, cocaine enters the tiny space where one nerve cell almost touches another, a sort of no man's land called the synaptic space.

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