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Gene therapy reduces drinking in "alcoholic" rats

UPTON, NY -- Scientists at the U.S. Department of Energy's Brookhaven National Laboratory have shown that increasing the level of a brain protein important for transmitting pleasure signals can turn rats that prefer alcohol into light drinkers, and those with no preference into near teetotalers. The findings, published in the first September 2001 issue of the Journal of Neurochemistry (Vol. 78, No. 5), may have implications for the prevention and treatment of alcoholism in humans.

"This is a preliminary study, but when you see a rat that chooses to drink 80 to 90 percent of its daily fluid as alcohol, and then three days later it's down to 20 percent, that's a dramatic drop in alcohol intake -- a very clear change in behavior," said Panayotis Thanos, the lead researcher. "This gives us great hope that we can refine this treatment for future clinical use."

The protein in question is the so-called D2 receptor for dopamine, a chemical that transmits brain signals necessary for experiencing feelings of pleasure and reward. Without receptors for dopamine, the signals get "jammed," and the pleasure response is blunted.

Previous studies have shown that alcohol abuse and other addictive drugs increase the brain's production of dopamine. But, over time, these drugs also deplete the brain's D2 receptors. This research has suggested that alcoholics increase their intake to try to override the blunted pleasure response, and that people with low levels of D2 receptors may be predisposed to alcohol abuse. These ideas led the Brookhaven researchers to hypothesize that increasing the level of D2 receptors might decrease alcohol intake.

The researchers tested this hypothesis in experimental rats by injecting a virus that had been rendered harmless and altered to carry the D2 receptor gene directly into the rats' brains. The idea behind this gene therapy is that the virus acts as a vector or mechanism to deliver the gene to the brain cells in the nucle
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
5-Sep-2001


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