Sex deprived fruit flies seek solace in drink

In experiments seeking to understand the root causes of human addiction, UCSF scientists have discovered that male fruit flies turn to alcohol when female flies reject their sexual advances.

When the researchers introduced male fruit flies to sexually receptive virgin females, the successful males drank very little alcohol. But when the females rejected their courtship efforts, the males drank to excess.

The research team attributed the behavior to a widely known chemical in the brains of male fruit flies called neuropeptide F, which the scientists found varies in brain levels depending on the degree of the males' success - or rejection - when seeking sex.

Taking their experiments a step further, the scientists, who have long used fruit flies successfully as a model for human behavior, presented decapitated female flies to a group of eager males.

Deprived of sex even without being subjected to outright rejection, the male flies drank even more heavily, they found.

Human relevance

Ulrike Heberlein, a professor of anatomy and neurology who led the experiments, said the research should ultimately prove relevant to problems of human addiction. Details of her team's work were published Friday in the journal Science.

The human brain carries a chemical similar to neuropeptide F, which is called neuropeptide Y.

When the scientists elevated the level of neuropeptide F in the brains of virgin male flies, they acted as if they were sexually satisfied, and drank much less.

Lowering the neuropeptide levels in the brains of sexually satisfied flies resulted in the flies behaving as if they had been rejected, and they drank heavily, the researchers observed.

The scientists reported that no direct connection between neuropeptide Y in humans and their alcohol behavior has been established, but Heberlein said in an interview that one long-term goal would be to see whether medications based on the human peptide might help addicted patients.

"First," she said, "we would have to show the same effects in rodents, and there we can manipulate them. But it will be much, much more difficult to translate the work to humans."

Dr. Markus Heilig, clinical director of the National Institute on Alcohol Abuse and Alcoholism and of the National Institute on Drug Abuse, called the Heberlein report "an extremely elegant paper, and a highly innovative approach to understanding the complex behaviors in alcohol abuse."

Insight to treatment

In a phone interview from his office in Bethesda, Md., Heilig said his colleagues have already considered the possibility of manipulating human neuropeptides as potential treatments for both alcohol and drug abuse.

"But so far the chemists have been unable to develop such drugs based on the neuropeptides," he said.

In San Francisco, David E. Smith, an addiction specialist and founder of the Haight Ashbury Clinics, was enthusiastic about the Heberlein study, as well.

"This kind of science is incredible," Smith said after reading the report. "Understanding the changes in the brain chemistry of model animals as they become addicted is where the action is today."

But Marc Wallis, a San Francisco psychotherapist who treats patients with substance use problems, was skeptical of the report's significance.

"Flies don't have a developmental history," he said. "They don't experience emotions, they don't have relationships, and they don't make meaning out of their experience. I don't believe we can de-psychologize substance abuse.

"Human problems such as substance abuse exist in an interpersonal context, and I believe that any treatment for substance abuse has to include a therapeutic relationship between people."

The fruit flies used in the experiments are familiar to generations of college biology students as Drosophila melanogaster. In the experiments, the flies had access to alcohol mixed in sugar water that they sucked from the ends of thin tubes.

Heberlein's team included UCSF researchers Galit Shohat-Ophir, Karla Kaun and Reza Azanchi.