Brain chemical affects alcohol sensitivity.

Concentrations of a natural chemical in the brain may influence how the body handles alcohol consumption, a new study shows.

Mice genetically engineered to lack neuropeptide Y, or NPY, a modulator of brain activity, shrug off the sedative effects of alcohol faster than normal mice and are apt to drink more of it when given the chance, researchers at the University of Washington in Seattle report in the Nov. 26 Nature. Conversely, mice with an overabundance of NPY in their systems recover from alcohol's effects more slowly and aren't as inclined to drink it.

People also produce NPY. The characteristics of NPY-deficient mice bear a provocative resemblance to behavior seen in alcoholics, says study co-author Todd E. Thiele.

"It's far too soon to make conclusions, [but] it's a very interesting possibility that in human alcoholics, low NPY levels in the brain may--at least in part--contribute to alcoholism," he says.

"It's a stretch, but an unavoidable one," agrees Enoch Gordis, director of the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Md. Previous research has found that college-age drinkers who aren't very sensitive to alcohol's effects have a higher incidence of alcoholism at age 30. "Reduced sensitivity to alcohol ... is pretty well established as a risk factor," he says. "We really don't know why."

Thiele and his colleagues gave 11 NPY-deficient mice and 11 normal mice access to two spigots--one dispensing water and the other water plus alcohol. With 10 or 20 percent alcohol mixes available, the NPY-deficient mice drank 30 to 50 percent more alcohol as did the normal mice. With a 6 percent mixture, the NPY-deficient mice drank twice as much alcohol as the control animals. Mice genetically engineered to have extra NPY drank less alcohol than did the controls.

In another test, the researchers injected seven NPY-deficient mice and seven of their normal littermates with a dose of alcohol large enough to put them to sleep for up to an hour. The deficient mice woke up and righted themselves on average 15 minutes sooner than the controls. Mice with additional NPY awoke later than normal mice.

The neuropeptide plays a role in appetite and anxiety. In this study, while no appetite difference appeared, mice lacking NPY tended to exhibit more anxiety, hiding out in dead-end corners of a maze, Thiele says. "One possibility is that these mice drink more alcohol to sort of self-medicate to help deal with anxiety levels that are high," he speculates.

"That cannot be ruled out," says Luis de Lecea, a molecular neurobiologist at the Scripps Research Institute in La Jolla, Calif. However, he notes that in the study mice having an overabundance of NPY didn't show unusually low anxiety.

"The important aspect of this study is that it opens up a new class of compounds in relation to alcohol--the peptide system," Gordis says. "This is an area [of research] which may be very productive."