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Flies, mice, rats offer addiction clues

By
ED SUSMAN, UPI Science News

ORLANDO, Fla., Nov. 4 (UPI) -- Clues developed by studying the genetic makeup of fruit flies, genetically-engineered mice and rats could lead to medical treatments for alcohol and drug addictions, researchers reported Monday.

At the annual meeting of the Society for Neuroscience, doctors said they have found a gene in mice -- also found in humans -- that when blocked makes addiction almost impossible and also eases drug withdrawal symptoms.

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"When we fed these mice morphine, they couldn't have cared less if they ever had it again," said Anthony Basile, a researcher at Alkermes, a drug development company in Cambridge, Mass.

The mice were created through genetic-engineering technology to have a missing brain gene, a protein called the muscarinic-5, or M5, receptor, which was discovered about 10 years ago.

Basile and colleagues then gave these so-called "knockout mice" and normal mice chow containing morphine. As expected, the normal mice came back looking for more, but the knockout M5s were not interested at all, he said. Even if the knockout mice were force-fed morphine to make them addicted, they exhibited fewer withdrawal symptoms than the normal mice.

If the M5 function in humans works the same way, then pharmaceutical companies might be able to create an M5 blocking agent that would give drug addicts a possible avenue of escape from their habit, he said.

"However, there are probably hundreds of genes that play a role in the addiction process," Basile said, suggesting something more than simply blocking one pathway might be required.

Those other pathways are what Ulrike Heberlein, assistant professor of anatomy at the University of California, San Francisco, is trying to find in the genetic makeup of fruit flies.

Although the idea of studying fruit flies to learn about human addiction might seem strange, Heberlein told reporters at a news briefing, "about two-thirds of the genes in the fruit fly Drosophila are the same as in humans," she said.

Her research has found giving flies the same proportional amount of alcohol that produces euphoria in people makes the insects hyperactive. If given the same proportion of alcohol that makes humans drunk, the flies cannot fly -- although the flies -- like humans -- can learn how to tolerate booze.

Heberlein said some of the genes in flies involved in alcohol use have been identified. "These genes will hopefully become candidate genes for genetic studies of alcoholism in humans," she said.

Another researcher, Barry Everitt, professor of behavioral neuroscience at the University of Cambridge, England, is exploring neural networks in rats that appear to be involved in drug-seeking habits. He said the animal research could lead to greater understanding of how certain parts of the brain work in people and how that function results in addictive behavior.

"The importance of this research becomes apparent when you look at addiction treatment today and realize that it is not adequate," said Dr. Eric Nestler, chairman of psychiatry at the University of Texas Southwestern Medical Center at Dallas. Breakthrough treatments of other diseases come from understanding the biology of the disease, he added.

Nestler said he thinks animal research has the potential to help prevent addiction, to help stop the process of addiction in people who are already dependent on substances and may help blunt the extent of addiction in others further down the addiction pathway.

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