Gene therapy technique reduces alcohol consumption in rats

Scientists at the U.S. Department of Energy's Brookhaven National Laboratory report in the current Journal of Neurochemistry (Volume 78, Number 5) that they used gene therapy techniques to increase levels of dopamine D2 (DRD2) receptors and reduce drinking in rats previously trained to self-administer alcohol. Panayotis Thanos, Ph.D., Nora Volkow, Ph.D., and colleagues used a partially inactivated virus as a vector, or transport agent, to carry copies of the DRD2 gene to the rat nucleus accumbens, the brain area associated with the reinforcing effects of alcohol. Supplying copies of the gene in this manner enables the rat brain cells to manufacture larger amounts of DRD2 receptors than they would ordinarily.

Strong evidence from pharmacologic studies in both humans and animals indicates that the dopamine pathway plays a major role in brain reward circuits, the function of which is altered by addiction. Whereas a drink of alcohol increases immediate brain production of dopamine (a chemical messenger, or neurotransmitter, involved in locomotion, alcohol reward, and the compulsion to drink) chronic drinking has been associated with decreased dopamine activity in rodents and with low levels of dopamine and its metabolites in humans. In 1996, Dr. Volkow and others showed that DRD2 receptors are depleted in human alcoholics. Whereas behavioral effects of this depletion are unclear, Drs. Thanos and Volkow hypothesize that DRD2 depletion produces a blunted pleasure response that leads alcoholics to increase their intake.

The research team performed two experiments for the current study-one to evaluate the rats' DRD2 receptor levels and one to evaluate drinking behavior at different time points following the DRD2 gene injection. To determine whether receptor levels had increased, they used a signal-emitting system designed to bind to the receptors and detected the signals in brain images known as autoradiographs. The strength of the signals indicated that ra

Contact: Ann Bradley
NIH/National Institute on Alcohol Abuse and Alcoholism

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