“Sexually deprived male fruit flies exhibit a pattern of behavior that seems ripped from the pages of a sad-sack Raymond Carver story: when female fruit flies reject their sexual advances, the males are driven to excessive alcohol consumption, drinking far more than comparable, sexually satisfied male flies.
Now a group of scientists at the University of California, San Francisco (UCSF) has discovered that a tiny molecule in the fly’s brain called neuropeptide F governs this behavior—as the levels of the molecule change in their brains, the flies’ behavior changes as well.
The new work may help shed light on the brain mechanisms that make social interaction rewarding for animals and those that underlie human addiction. A similar human molecule, called neuropeptide Y, may likewise connect social triggers to behaviors like excessive drinking and drug abuse. Adjusting the levels of neuropeptide Y in people may alter their addictive behavior—which is exactly what the UCSF team observed in the fruit flies.
“If neuropeptide Y turns out to be the transducer between the state of the psyche and the drive to abuse alcohol and drugs, one could develop therapies to inhibit neuropeptide Y receptors,” said Ulrike Heberlein, PhD, a Professor of Anatomy and Neurology at UCSF, who led the research.
Clinical trials are underway, she added, to test whether delivery of neuropeptide Y can alleviate anxiety and other mood disorders as well as obesity.
A Reward Switch in the Brain
The experiments, described this week in the journal Science, started with male fruit flies placed in a container with either virgin female flies or female flies that had already mated. While virgin females readily mate and are receptive toward courting males, once they have mated, females flies lose their interest in sex for a time because of the influence of a substance known as sex peptide, which males inject along with sperm at the culmination of the encounter. This causes them to reject the advances of the male flies.
The rejected males then gave up trying to mate altogether. Even when placed in the same cage as virgin flies, they were not as keen to have sex. Their drinking behavior also changed.
When placed by themselves in a new container and presented with two straws, one containing plain food and the other containing food supplemented with 15 percent alcohol, the sexually rejected flies binged on the alcohol, drinking far more than their sexually satisfied cousins whose advances were never spurned. The difference was not only apparent in their behavior. It was completely predicted by the levels of neuropeptide F in their brains.
“It’s a switch that represents the level of reward in the brain and translates it into reward-seeking behavior,” said Galit Shohat-Ophir, PhD, the first author of the new study.
A former postdoctoral researcher at UCSF, Shohat-Ophir is now a research specialist at the Howard Hughes Medical Institute (HHMI) Janelia Farm Research Center in Ashburn, VA. Later this year, Heberlein will also move to Janelia Farm, where she will become scientific program director.