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November 25, 1998

Alcohol consumption, resistance to its effects related to levels of neurotransmitter, say UW researchers

Science is still a long way from understanding why some people are more prone to alcoholism and alcohol abuse than others, but University of Washington researchers have discovered that concentrations of a neurotransmitter in the brains of mice are directly related to alcohol consumption and resistance to the sedative effects of alcohol.

Writing in tomorrow’s issue of the journal Nature, the UW scientists report that genetically altered mice that do not produce the naturally occurring brain chemical or neurotransmitter called neuropeptide Y (NPY) drank significantly more alcohol and were less affected by its sedative, or sleep-inducing, effects than normal mice. In addition, genetically engineered mice that produce abnormally high levels of NPY drank less alcohol than normal mice and were highly prone to succumb to its sedative effects.

“This is the first direct demonstration that there are altered levels of alcohol consumption if you change the amount of NPY present in the brains of rodents,” said Todd Thiele, who headed the UW team along with Richard Palmiter. “Alcohol consumption and resistance are inversely proportional to concentrations of NPY in the brain. Together, these data indicate that in rodents there is a relationship between NPY levels and the willingness to voluntarily consume alcohol.”

The researchers cautioned that while their results with mice are convincing, further research is necessary to determine if there is a relationship between NPY and alcohol consumption and abuse in humans. They next plan to try to find the mechanism by which NPY in the brain modulates alcohol drinking.

“This study is important for two reasons,” according to Dr. Enoch Gordis, director of the National Institute on Alcohol Abuse and Alcoholism. “It indicates that peptides related to appetite and anxiety are significant areas for study in alcohol research and that drugs designed to interact with components of the neuropeptide Y signaling system may someday be useful in helping individuals control their alcohol consumption.”

To measure the effects of NYP levels on alcohol consumption in mice, the UW scientists set up a regimen in which mice were individually housed and given food plus water in two bottles. Next water in one of the bottles was replaced with ethanol solutions in increasingly stronger concentrations of 3, 6, 10 and 20 percent. The animals were given each ethanol solution for eight days and their alcohol consumption was monitored. The 3 percent alcohol solution is roughly equivalent to a beer while the 20 percent solution is about half as powerful as a shot of whiskey.

Thiele also noted that the sedative effects of alcohol on the two genetically altered strains of mice were strikingly different. While the mice with no NPY drank significantly more alcohol than normal mice, they woke up more quickly from alcohol-induced sleep than the animals with standard levels of the neurotransmitter. The case was just the opposite with mice with high brain levels of NPY. Even though they drank significantly less alcohol, they took a lot longer to wake up after drinking ethanol than normal mice.

Thiele is a research scientist in the psychology department at the UW and Palmiter is a professor of biochemistry and an investigator with the Howard Hughes Medical Institute. Other members of the research team are Donald Marsh, a post-doctoral researcher in Palmiter’s laboratory; Ilene Bernstein, professor of psychology; and Linda Ste. Marie, a doctoral candidate in biochemistry. The research was funded by the National Institute on Alcohol Abuse and Alcoholism and the Howard Hughes Medical Institute.
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For more information, contact Thiele at (206) 685-1743 or thiele@u.washington.edu