'Happyhour' Gene May Help Put Boozers Off Their Drink

May 23, 2009— -- A newly identified gene called happyhour makes fruit flies sensitive to booze. Drugs that mimic the effects of the gene may offer a new treatment against alcohol abuse, researchers say.

"People who are very sensitive to alcohol tend to drink less – that's the person who gets drunk on one glass of wine," says Robert Swift, a psychiatrist at Brown University in Providence, Rhode Island, who was not involved in the new study.

"The person who can drink everybody under the table – that's that person who is more likely to become an alcoholic," he adds.

When they drink, laboratory fruit flies aren't so different from pub-crawlers on a Friday night. "They go through a phase of hyperactivity and they gradually become uncoordinated; they stop moving and they fall over; and eventually they are unable to right themselves," says Ulrike Heberlein, a molecular biologist at the University of California, San Francisco, who led the new study.

Bar Flies

Heberlein and colleague Ammon Corl hunted for mutant fruit flies able to keep the party going and not pass out.

Two strains of flies fit this description, and both carried mutations in a gene that Heberlein's team dubbed happyhour.

In 1998, Heberlein's lab published a paper identifying a mutation that makes flies super-sensitive to alcohol in a different gene and named those mutants cheapdate. And flies missing a gene called hangover did not develop an increased tolerance for alcohol common among seasoned drinkers, her team revealed in 2005.

The happyhour gene, Heberlein's team has discovered, dampens a well-studied cellular network involved in cell division and implicated in cancer, called the epidermal growth factor (EGF) pathway.

When the researchers switched happyhour back on in brain cells of mutant flies, they got drunk like normal flies. In particular, neurons that respond to a brain chemical called dopamine seemed to cause the alcohol-sensitive effects of happyhour.

Treatment Hope

Dopamine has a well-characterised role in drug use, so that could explain the connection to happyhour, Heberlein says. Yet the neurotransmitter is also involved in movement, and more research will be needed to determine how happyhour contributes to alcohol sensitivity, she adds.

A new treatment for alcohol abuse may not have to wait for this research, however. The US Food and Drug Administration has already approved several cancer drugs that block the EGF pathway.

Heberlein's team tested two of those medicines, erlotinib and gefitinib, on normal flies, and found that they were more likely to be knocked out by alcohol than flies that did not take the drugs. Mice that took erlotinib showed the same effects when they drank.

More impressively, rats that had developed a taste for alcohol chose to drink less booze after Heberlein's team gave the rodents erlotinib. They still maintained an appetite for sugar, suggesting their ability to sense food rewards hadn't been completely demolished by the drug.

"I'm very much looking forward for it to be tested in humans, and it's quite possible one wouldn't need the doses used in chemotherapy to treat addicts," Heberlein says.

Reversible Habit?

Rats showed few side effects, and the most common side effect of the drugs in humans is skin rash, according to the FDA.

Most of the drugs approved to treat alcohol abuse target brain chemicals involved in addictive behaviour, says Swift. Generally, doctors combine these medications with therapy.

"Theoretically, a medication that increases the sensitivity to alcohol – that you need to drink less of to get an effect – might be protective," he says.