A newly identified gene, dubbed happyhour, controls fruit flies' response to booze. Researchers now claim that drugs mimicking the effects of the gene may offer a new treatment against alcohol addiction.
Animals with a mutant version of the gene grow increasingly resistant to alcohol's sedative effects, the research shows.
The researchers report further evidence that the gene normally does its work by blocking the so-called Epidermal Growth Factor (EGF) pathway. That EGF pathway is best known for its role in cancer, and drugs designed to inhibit the EGF receptor, including erlotinib (trade name Tarceva) and gefitinib (trade name Iressa), are FDA-approved for the treatment of non-small cell lung cancer.
Now, the researchers show that flies and mice treated with erlotinib also grow more sensitive to alcohol. What's more, rats given the cancer-fighting drug spontaneously consumed less alcohol when it was freely available to them. Their taste for another rewarding beverage-sugar water-was unaffected.
"This is a very powerful example of how simple model organisms-and the little fruit fly in particular-can be used to move quickly from an unknown gene to a potential therapy for drug addiction," said Ulrike Heberlein of the University of California, San Francisco, noting that erlotinib and gefitinib, along with other EGFR inhibitors, not only cross the blood-brain barrier in humans, but they are also well-tolerated in general.
Heberlein's team explained, genes and pathways involved in the acute response to alcohol can yield insight into the genetic factors contributing to the more complex process of addiction.
In the study, researchers screened mutant flies for those less sensitive to ethanol. That screen led them to happyhour, a gene closely related to mammalian enzymes known as the Ste20-family kinases of the GCK-1 subfamily.
Heberlein said they still don't know exactly how alcohol exerts its influence on the EGFR pathway or how that leads to the telltale changes in behavior that come with alcohol intoxication.