Male fruit flies whose sexual advances are rejected by females, turn to alcohol finds a new study. Scientists at the University of California, San Francisco discovered that rejected male flies have a tiny molecule in their brain that pushes them to drink far more than their sexually satisfied counterparts. The levels of the molecule, neuropeptide F, were higher in sexually satisfied males than in those who got no sex, leading scientists to speculate that their work could shed light on brain mechanisms behind human addiction. A similar human molecule - neuropeptide Y - may also link social triggers to behaviors such as heavy drinking and drug abuse, according to the study published in Science journal.
“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 lead researcher Ulrike Heberlein, a professor of anatomy and neurology at UCSF. She said clinical trials were under way to determine whether neuropeptide Y can alleviate anxiety and other mood disorders as well as obesity.
The researchers for the experiment used male fruit flies (Drosophila melanogaster) that were placed in a container with females flies, including both virgins and some that had mated. Virgin females were receptive to courting males and readily mated, but females flies who had mated lost interest in sex for a time because of sex peptide, a substance that males inject with sperm during the encounter.
Rejected males then stopped trying to mate, even when placed in the same cage as virgin flies. But when they were placed by themselves in another container that had two straws - one containing plain food and the other containing food with 15 per cent alcohol - the rejected males binged on the alcohol.
The scientists said the behavior was 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 behaviour,” said lead author Galit Shohat-Ophir of the Howard Hughes Medical Institute Janelia Farm Research Center in Virginia. Rejected flies had lower levels of neuropeptide F and sought an alternative reward through intoxication.
The scientists found they could induce the same behaviors in the flies by genetically manipulating the levels of neuropeptide F in their brains. Activating neuropeptide F production in the brains of virgin male flies caused them to behave as though they were sexually satisfied, and thus they were less keen to drink. And lowering the levels of the molecule in sexually satisfied flies made them behave as though they were rejected, inciting them to drink more.
“We wanted to really find a molecular mechanism that links experiences to drug-related behavior,” said Heberlein. “We are really hoping that this will encourage those working with mice and rats and humans to look at what happens to this neuropeptide in psychiatric conditions.”
“This is an amazing link,” said neurogeneticist Troy Zars of the University of Missouri, Columbia, who was not involved in the study. Understanding the brain pathways responsible, he says, could help explain more broadly how rewarding behavior is reflected in the brain, and how the brain mediates complex behaviors.
“Reading this study is like looking back in time, to see the very origins of the reward circuit that drives fundamental behaviors like sex, eating and sleeping,” said Dr. Markus Heilig, the clinical director of the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. Dr. Heilig, who was not involved in the research, said the findings also supported new approaches to treating alcohol dependence. Researchers are investigating several compounds aimed at blunting alcohol urges.
Previous studies have found that NPY is involved in a wide range of behaviors, like eating, sleeping and response to stress. But the new study, and others, suggest that scientists could reduce drinking by developing drugs that enhance the activity of NPY, said George Koob, a professor of neurobiology and addiction at the Scripps Research Institute in La Jolla, Calif. “The study implies that it is this system that goes haywire in addiction,” Dr. Koob said, “and that it’s very sensitive to stress. For instance, after you lose a loved one, or a relationship has crashed, you get dysphoric, your NPY goes down, and this provides a strong urge to drink a lot — whether you’re a mammal or a fruit fly.”
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