Drunk as a fly

The discovery could lead to a treatment for alcoholics

Scientists have discovered that drunken flies behave in the same way as inebriated humans. The scientists also found that the flies' response to alcohol can be reversed with a drug. This may eventually give clues as to how to treat alcoholism in humans. Pauline Newman of BBC Science reports

Alcohol is one of the most widely abused drugs in the world, yet little is known about how it acts on the brain to make people drunk.

There is lots of evidence to show that people's response to alcohol is genetically influenced - young men with a family history of alcoholism often get drunk less quickly and yet are more likely to go on to become alcoholics than young men from families without an alcohol problem - but the genes responsible have never been identified.

A similar situation is found in animals that have been studied in the laboratory, such as mice and rats. And in the wild, elephants and bats have been seen to get drunk on fermenting fruit. Now American researchers have discovered that insects are susceptible to alcohol too.

Professor Ulrike Heberlein and her colleagues from the University of California at San Francisco have found that fruit flies can get drunk, and when they do so, they behave just like inebriated humans.

"We never imagined that these tiny little fruit flies would show behaviours that are so similar to what you find in higher animals and even in humans when they become intoxicated," Professor Heberlein said.

"You can observe them become hyperactive and then disorientated and then they become quite unco-ordinated and sedated and eventually pass out. If you look at the course of what might be called a drinking bout in a fly, it really goes through the same phases as in a bigger animal."

Just like humans, flies differ in their response to alcohol. Some individuals, or mutants, get drunk very quickly. Others, who may correspond to human alcoholics, are more resistant to the effects of alcohol.

Some flies drink more than others

To study the flies' behaviour, Professor Heberlein used a tall glass column containing a series of rings, or baffles, that the flies would perch on. Their favourite position was the top rung. Then she filled the column with alcohol vapour and watched what happened.

"As the flies gradually become intoxicated and unco-ordinated, they start falling through this column and eventually come out at the bottom of the column. Normal flies will come out in about 20 minutes, but we can isolate mutants which come out earlier, for example at 15 minutes instead of 20 minutes. These flies would be sensitive to ethanol [alcohol]. We also have mutants that come out later, at maybe 30 minutes. So by running the flies through these columns and testing their ability to hold on to the baffles we can identify mutants that are more, or less affected by alcohol."

Professor Heberlein's team next looked at what was happening in the flies brains and discovered a form of a gene, which they called Cheapdate, that controls the flies response to alcohol.

A different form of this gene was already known to be responsible for memory in flies. The gene works by regulating the pathway of a signalling chemical called cyclic AMP that is central to many processes in the body, including memory and learning. This pathway also determines how the flies respond to alcohol.

Their inebriation was reversed when the scientists gave them drugs to block the pathway. Although humans don't seem to have the Cheapdate gene, they do have the cyclic AMP pathway. This raises the possibility that we may one day be able to use drugs to regulate people's susceptibility to alcohol.

"I think that this is the very first step in a general approach that we hope will lead to that. We were able to give these mutant flies some drugs that reversed their behaviour and made them normal again when they were exposed to alcohol. I'm sure that we can't use those same drugs in humans because they would probably be toxic.

"However, in the long-term, I would imagine that drugs that act more specifically could be used in this kind of treatment."