NIH News Release
National Institute on Drug Abuse

Monday, April 23, 2001
5:00 p.m. EST

Beverly Jackson, Michelle Muth
Blair Gately (301) 443-6245

Study Clarifies Brain Mechanisms of Cocaine's High
A team of researchers led by scientists from the National Institute on Drug Abuse's Intramural Research Program has made a major advance in understanding the molecular basis of how cocaine produces its characteristic high, suggesting new targets for developing anti-addiction medicines. The findings, published in the April 24 issue of the Proceedings of the National Academy of Sciences, show that inactivating both the serotonin and dopamine transporters in the brains of mice dramatically reduces their experience of cocaine's rewarding, pleasurable effects. It has been known for some time that cocaine use affects the brain's dopamine system, but also that manipulating dopamine does not fully control cocaine's effects. Thus this study shows the critical importance of the serotonin system as well as the dopamine system in mediating cocaine's pleasurable effects.

"Currently, there is no medication that effectively blocks the brain's reward response to cocaine or that substantially relieves cocaine addiction, " says NIDA director Dr. Alan I. Leshner. "The finding that serotonin as well as dopamine plays a critical role in the development of cocaine addiction suggests a new biological target and approaches for developing such medications."

Dr. George Uhl, head of the NIDA research team, explains that his team studied genetically altered mice that were missing one or both copies of the dopamine transporter (DAT) and serotonin transporter (SERT) genes. They found that mice with even a single DAT gene copy and no SERT copies still experienced reward/reinforcement following cocaine administration. However, cocaine-induced reward/reinforcement behavior was totally blocked in mice with no DAT gene and either half-normal or absent SERT. Dr. Uhl says, "These results demonstrate the dependence of cocaine reward on both DAT and SERT blockade. They define for the first time the brain molecular targets necessary for cocaine reward. They suggest that drugs acting on both dopamine and serotonin brain systems might be needed to effectively combat cocaine addiction."

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish through NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at