September 1, 1999

Brookhaven Lab and SUNY Stony Brook Researchers
Find Chemical Clues to Drug Abuse Vulnerability

UPTON, NY - Why do some people who experiment with drugs become addicted, while others do not? Researchers at the U.S. Department of Energy's Brookhaven National Laboratory and the State University of New York (SUNY) at Stony Brook made significant progress in answering that question in a study to be published in the September 1 issue of the American Journal of Psychiatry.

This Brookhaven/SUNY Stony Brook study is the first to show a link between dopamine receptors in the brain and reinforcing responses to psychostimulants in humans. Dopamine receptors are the sites in the brain that transmit signals associated with pleasure and reward.

Twenty-three healthy male subjects who had occasional experience with drugs of abuse but who did not abuse them were given an intravenous dose of Ritalin, which is a psychostimulant drug used in the treatment of attention deficit disorder. The drug can cause euphoria when it is injected. The subjects' response to the stimulant was assessed through self-reported effects of the drug, and through a brain-imaging technique known as positron emission tomography (PET). Specifically, PET images showed the quantity of each subject's dopamine receptors.

The effects of the injected drug were varied among the 23 subjects, and they were correlated with brain chemistry. The 12 men who described the effects of Ritalin as pleasant had significantly fewer dopamine receptors than the nine men who found the drug's effects to be unpleasant. Two men said the drug had no effect on them. The research verified earlier studies of laboratory animals, which showed an association between positive, reinforcing responses to drugs of abuse and fewer dopamine receptors. The researchers postulated that fewer dopamine receptors could predispose a subject to use drugs as a means to compensate for decreased activation of reward circuits in the brain.

Dr. Nora Volkow, Brookhaven's Associate Laboratory Director for Life Sciences and the lead author of the study, commented, "We know from past studies that drug addicts and alcoholics have fewer dopamine receptors than people who are not addicted to drugs or alcohol. In our current research, subjects who were not drug abusers and reported the effect of the stimulant as pleasant - as most cocaine abusers do - had dopamine levels similar to those in cocaine abusers. Thus, the hypothesis that people with fewer dopamine receptors may take drugs to activate these pleasure circuits may be one of the factors that predisposes a person to drug abuse. Other biological as well as genetic and environmental factors are likely to contribute to the susceptibility to drug abuse and addiction."

Alternatively, fewer dopamine receptors could predispose a person to drug abuse by favoring initial pleasurable drug responses, which have been shown in past studies to predict future drug use. Additionally, a high number of dopamine receptors may protect against drug abuse by favoring unpleasant drug responses. Further studies will be needed to determine more precisely how dopamine receptors affect the predisposition to drug abuse.

This study was funded by the National Institute on Drug Abuse and the U.S. Department of Energy. These studies were done following the guidelines set forth by the Institutional Review Board at Brookhaven National Laboratory.

The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences, and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for-profit research management company, under contract with the U.S. Department of Energy.

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