October 7, 1999

Brookhaven Lab and SUNY Stony Brook Researchers
Link a "High" from Drugs to Brain Biochemistry


UPTON, NY - Researchers from the U.S. Department of Energy's Brookhaven National Laboratory and the State University of New York at Stony Brook have gained new insight into the biochemistry of the reward circuits in the brain that are related to drug addiction. In a study of human volunteers, the researchers have determined that dopamine, a chemical associated with pleasure and reward, surges in certain areas of the brain when subjects experience a "high" from an injected dose of Ritalin, a drug commonly prescribed to treat hyperactive children.

The results of the study are published in the October issue of the Journal of Pharmacology and Experimental Therapeutics.

"Previous animal studies have shown a positive correlation between dopamine and the reinforcing effects of psychostimulant drugs, but this is the first human study that proves it," said psychiatrist Nora Volkow, lead author in the study. Since the high derived from an intravenous dose of Ritalin is similar to the euphoric high experienced by cocaine abusers after they take a dose of cocaine, she added, "These results support the development of drugs that treat cocaine addiction by interfering with cocaine-induced increases in dopamine."

The researchers also reported that the euphoria derived from taking psychostimulant drugs is correlated with the interaction of dopamine in the brain with the dopamine receptors involved with movement and reward. Dopamine receptors transmit signals from dopamine into brain circuits that trigger various sensations.

According to Volkow, the dopamine receptors in those subjects who experienced a high, regardless of the dose of the drug they were given, were filled with dopamine by more than 15 percent.

Fourteen healthy adults - eight males and six females - who did not have a history of drug or alcohol abuse were given either intravenous doses of Ritalin or a placebo, at specified intervals. Using an imagining technique called positron emission tomography, the researchers first took brain scans of those who were administered the placebo and, about two hours later, took brain scans of subjects who had ingested Ritalin.

Each subject's self-reported reaction to the drug was also recorded and evaluated on a scale from 0 (felt nothing) to 10 (felt intensely). These recordings took place five minutes before the placebo or Ritalin was administered, then every minute for the first 20 minutes, and then at longer intervals, up to 67 minutes.

In general, the subjects' reaction to Ritalin was related to the amount of dopamine released into the brain after Ritalin was administered. While the researchers found, in every case, an increase in dopamine in the brains of those who felt euphoria from Ritalin, those who did not feel high had no change in the dopamine levels in the brain.

The researchers also found variability in the feelings of euphoria, however, that could not be completely accounted for by the amount of Ritalin administered. This could be the result of limitations of the experimental procedures, but also differences in dopamine receptor sensitivity among individuals. Additionally, other brain chemicals, such as serotonin, may come into play in determining the response to psychostimulant drugs.

This study was funded by the National Institute on Drug Abuse, the Office of National Drug Control Policy 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, which regulates experiments on humans.

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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