The researchers exposed fruit flies to vaporized alcohol and monitored their behavior and motion patterns with sensitive tracking instruments. They isolated the flies that were less sensitive to alcohol's sedative effects. By breeding subsequent populations of mutant flies, the scientists identified the particular genetic mutation.
The researchers further showed that the white rabbit mutation disrupted the function of the RhoGAP18B gene. They also isolated a number of gene variants of RhoGAP18B, each of which had a distinctly different effect on the response to alcohol. Manipulating these genetic variants, the researchers generated flies with greater and lesser sensitivity to alcohol's sedative and stimulant effects.
The research team also detailed how signaling proteins encoded by the RhoGAP18B gene variants played an important role in reorganizing components of the adult fruit fly's central nervous system, which in turn affected the flies' behavior. Dr. Rothenfluh said the research team concluded that the RhoGAP18B gene is intimately involved in regulating behavioral responses to alcohol exposure.
The findings have implications for researchers seeking corresponding genes and molecular pathways in other animal models and humans. Antonio Noronha, Ph.D., director of NIAAA's Division of Neuroscience and Behavior, said, "If we can characterize similar genetic differences and neurobehavioral responses that underlie acute tolerance in humans, that could potentially provide new targets for the development of drugs to treat alcohol dependence."