Enzyme May Offer New Target for Treatment of Alcoholism
Oct. 18, 1999 (Indianapolis) -- Researchers from the University of California, San Francisco, have identified an enzyme that might one day become useful in the treatment of alcoholism. Their report, published in the November issue of Nature Neuroscience, shows that mice genetically engineered to lack the enzyme PKC epsilon were 75% less likely to drink alcohol in a self-administered test than were mice with the enzyme.
"Studies have shown that the brain chemical GABA is involved in the rewarding properties of alcohol," says Clyde Hodge, PhD, from the Ernest Gallo Research Center at UCSF. There are receptors on brain cells that use GABA as the way to signal the brain to feel relaxed, gratified, or sedated. Alcohol and a group of drugs known as benzodiazepines, such as Valium, Xanax, and Ativan, work with GABA to make the signals stronger and last longer.
The researchers found that in the mice without the enzyme, the GABA receptors were more sensitive to alcohol. That heightened sensitivity actually decreased the craving for alcohol. Hodge tells WebMD, "We first wanted to know if the mice would self-administer less alcohol if the PKC epsilon enzyme was missing and then try and find out why it occurred."
"This may turn out to be a novel way to target for the development of drugs to treat some of the reward aspects of alcoholism," Hodge says. "These mice also support the concept emerging in alcohol research that increased sensitivity to alcohol lessens the likelihood that a person will become an alcoholic."
Robert Karp, PhD, reviewed the study for WebMD. He says that the paper adds to the general understanding of the pathways in the brain that are involved in alcoholism. Karp is the program director for genetics at the National Institute on Alcohol Abuse and Alcoholism.
"This paper illustrates quite nicely that we have some powerful new tools that we can use to make advances," Karp says. "Long term, this study implies that perhaps drugs that inhibit PKC epsilon could serve as prototype medications against excessive alcohol consumption. This is a very good start toward that goal."