Researchers at the University of California, San Francisco (UCSF) have discovered a gene mutation in fruit flies that alters sensitivity to alcohol. The findings, reported in the October 6 issue of the journal Cell, may have implications for human studies seeking to understand innate differences in people's tolerance for alcohol. The research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services.

The study was authored by Adrian Rothenfluh, Ph.D., and colleagues in the laboratory of Ulrike Heberlein, Ph.D., at UCSF, in collaboration with researchers at the Ernest Gallo Clinic & Research Center. The scientists examined the behavior of fruit flies (Drosophila) exposed to alcohol. Ordinarily, at low doses of alcohol fruit flies increase their activity, while high doses have a sedative effect. However, the researchers found some fruit flies were much more resistant to alcohol sedation. These flies continued to move about much longer than typical fruit flies exposed to the same amount of alcohol. The scientists subsequently identified key differences in a particular gene associated with this behavior. The mutation also altered the flies' sensitivity to cocaine and nicotine as well. Because this gene variant affected the behavioral response to substances of abuse, the researchers dubbed it white rabbit--a reference to the title of a 1960s song about drug-induced changes.

"This study describes key molecular pathways and gene interactions that control alcohol sensitivity," said NIAAA Director Ting-Kai Li, M.D. "These significant clues about the fruit fly's behavioral response may translate into useful tools to advance the search for human genes involved in sensitivity to alcohol. Insights about sensitivity, or acute tolerance, are especially important because we know that peopl
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Contact: Gregory Roa
greg.roa@nih.gov
301-443-3860
NIH/National Institute on Alcohol Abuse and Alcoholism
5-Oct-2006