Research findings suggest compound might help in fight against alcoholism

By DAVID WILLIAMSON
UNC News Services

CHAPEL HILL -- Relapses remain among the toughest hurdles alcoholics face while trying to avoid the drinking that often ruins their lives and indelibly scars their families. The urge to drink excessively, which most people don’t feel at all, is enormously powerful in a significant minority of people.

Now scientists at the University of North Carolina at Chapel Hill have discovered something that might lessen the overwhelming compulsion to drink. Working with laboratory mice specially bred and trained to consume alcohol, they have shown for the first time that they can curb mice’s alcohol intake by treating them with a novel compound known as L-152,804.

Whether the compound will be effective and safe in humans has not been tested yet, they say. If it is found to work in future tests, it will block or neutralize the action of a kind of neurotransmitter -- chemicals that brain cells use to communicate with each other.

"The experimental compound L-152,804 blocks the actions of one particular neurotransmitter called neuropeptide Y," said lead researcher Dr. Clyde W. Hodge.

"This naturally occurring transmitter is the most abundant and widely distributed peptide in mammals’ central nervous systems," Hodge said. "Not only is it involved in anxiety, pain and memory, but it also is the most potent stimulant of feeding behavior known. Neuropeptide Y has been implicated in overeating and obesity as well as alcoholism during earlier studies, including one conducted in our laboratory."

Hodge is associate professor of psychiatry and pharmacology at the UNC School of Medicine’s Bowles Center for Alcohol Studies.

The compound L-152,804 slowed the beginning of alcohol consumption in mice with a genetic predisposition to drink and also cut its continuance, he said. Since L-152,804 blocks the actions of neuropeptide Y at a specific receptor called Y5, drugs that specifically target that receptor may have therapeutic potential for treating relapses, the new experiments showed.

A report on the research appears in the December issue of Alcoholism: Clinical & Experimental Research, the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Besides Hodges, authors include Dr. Jason P. Schroeder, research associate in psychiatry.

In their experiments, the scientists housed five dozen male mice in plastic cages with food and water always available. They trained the mice over four months to drink as much as they wished of either alcohol or water during 16-hour sessions.

After the four months, they injected the rodents with varying concentrations of L-152,804 and again observed and recorded their drinking behavior. Three different strengths of the compound significantly delayed alcohol consumption in the animals, some by as much as 900 percent, Hodge said.

"Most of the known compounds that target neuropeptide Y receptors do not cross a naturally protective barrier in the central nervous system known as the blood-brain barrier," he said. "However, this novel compound has been shown both to cross the blood-brain barrier and to block neuropeptide Y-Y5 receptors, which may be very good news in our attempts to curb alcoholism in humans."

The results suggest L-152,804 might reduce the motivation to start drinking as well as decrease the amount of alcohol consumed, Hodge said. Hence, it might make relapses less likely.

"When you consider that L-152,804 can be administered orally, we believe that medications that block neuropeptide Y actions at its receptors have great potential for the medical management of alcoholism," he said.

The National Institute on Alcohol Abuse and Alcoholism, the University of California at San Francisco through state appropriations, and the Bowles Center supported the research.

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Note: Hodge can be reached at (919) 843-4823

Media contact: David Williamson, (919) 962-8596