It’s the ultimate seedy bar scene: Late in the evening, a guy makes a move on a woman sitting on the next bar stool, who turns him down. Rebuffed, he turns to the bartender and drowns his sorrows in another beer. That scene has now been played out, not in a bar, but in a modern lab at the University of California at San Francisco, and not with people but with flies.
Male fruit flies, rejected in their attempts to mate, turn to alcohol-soaked food, researchers reported today in the journal Science. Scientists think the discovery, along with evidence that the behavior seems to be driven by a small molecule in the brain, may open a window onto the self-destructive actions of alcoholics and drug addicts.
The molecule, called neuropeptide F, “couples frustration and behavior in a way we hadn’t known about,” says Troy Zars, an associate professor of biological sciences at the University of Missouri at Columbia and an expert in fruit-fly behavioral genetics. A similar molecule has been linked to overeating and a liking for alcohol in mammals. Mr. Zars, who wasn’t involved with the research and wrote a commentary on it in the same issue of the journal, says the discovery of the molecule’s role “lets you think about drugs that act on it to reduce alcohol-seeking behavior.”
Ulrike Heberlein, a professor of anatomy and neurology at UCSF, and her colleagues created their fly-blown bar by putting male flies in containers with females that had just mated. In the cramped space, males pursued the females, but recently mated females are rarely receptive to such advances. The males then were given a choice of food: normal fly food, or a dish laced with 15 percent ethanol (a form of alcohol). They went for the ethanol-soaked food.
Their behavior was a lot different than that of a similar set of male flies who mated successfully. Those males didn’t show any preference for food type.
That wasn’t the only difference. When examined, the frustrated flies had low levels of neuropeptide F in a few specific neurons. The happily mated flies had much higher levels.
Then the researchers found they could change the alcohol-seeking behavior of the flies not just by changing their mating opportunities, but by changing their neuropeptide F levels. Increasing levels in the frustrated flies cut down on their preference for booze. Decreasing the levels in the mated flies actually made them act like the frustrated ones, and they hit the alcohol much more heavily.
The molecule seems to be a very important switch, notes Galit Shohat-Ophir, a study co-author who is a research specialist at the Howard Hughes Medical Institute’s Janelia Farm Research Center, in Ashburn, Va. No one is surprised that denial of a basic drive, like mating, leads a creature to seek alternate forms of stimulation, but neuropeptide F appears to be the crucial link that connects the two kinds of behavior. And the switch can be turned on and off, affecting the result.
“It’s a pretty complete story,” adds Mr. Zars, who notes that a similar molecule with a similar name, neuropeptide Y, has been found in mammals. But the switch effect hasn’t been found before, he says. The molecules seem to sit in between reactions to denial—in humans, not flies, those might be feelings like anxiety or depression—and behaviors that appear to make creatures feel better. When those behaviors are harmful, like alcoholism, he says that researchers could look for medications that act on the molecules, and use the switch to shut them down.