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Brain Protein Suppresses Craving for Alcohol

Alcohol addiction – alcoholism – is a problem found in every country and every culture. Millions of alcoholics try to stop drinking, but alcohol addiction is powerful. Many who try to quit relapse and begin drinking again. Rose Hoban reports on a new approach to treating alcoholism.

Molecular biologist Dorit Ron from the University of California at San Francisco says scientists have come up with drugs to treat conditions from heart disease to psychiatric disorders, but treatments for alcoholism are lacking. She and her research colleagues decided to investigate a neuroprotein known as GDNF, glial cell-derived neurotropic factor. GDNF is a protein that is made by brain cells both nerve cells and glial cells – a type of brain cells.

"It is released from these cells and it's very important for the development of the brain," Ron explains. "And it's very important to keep certain types of nerve cells alive and healthy."

Scientists became aware of GDNF because of side effects from a hallucinogenic drug called ibocaine that became popular in the 1960s. Researchers observed that when people took ibocaine, their brains produced more GDNF. At the same time, their cravings for alcohol virtually disappeared. But ibocaine has many toxic side effects, including fatal ones.

So Ron studied just the GDNF. She trained rats in her lab to drink alcohol; they were taught to press a lever and then go to a different location to get alcohol as a reward. Ron says she likes to call the alcohol-delivery system the 'rat bar.'

"[The rats] press a lever, [as if] the rat pays [for a drink], and then it goes and gets the drink," she says. "In one experiment, the rats got a 10% alcohol solution which resembles what social drinkers get. So it's resembles people going to a restaurant or bar and having a drink or two."

Ron gave the rats GDNF using a device to pump it directly to their brains. She says the effects were almost immediate.

"The rats that received GDNF did not press the lever for alcohol any more," Ron says. "Ten minutes after they received GDNF, they basically had no desire to consume alcohol."

But one of the problems with using GDNF to treat alcoholism is that the molecule is large. It's too large, in fact, to cross the blood brain barrier, a protective tangle of blood vessels and membranes that keeps toxins from reaching the central nervous system.

For humans, as with the rats, GDNF would have to be injected directly into the brain. Ron says her lab is looking at methods to circumvent the barrier.

"One is to develop small molecules that would resemble GDNF and that will cross the blood brain barrier and will be able to be given systemically," Ron says. "Another possibility is to use things like ibogaine – without, of course, the side effects – that will be given systemically and will increase the level of GDNF in the brain."

Ron says she's working on several compounds in her lab and says she has some promising results to be published soon. Her research into GDNF is published in the Proceedings of the National Academy of Sciences.