Mice Lacking Gene Show Reduced Alcohol Preference And Sensitivity

l. To make sure the mice were not simply avoiding the taste of alcohol, they were later given a choice between water and a saccharine (sweet) or quinine (bitter) solution. The location of the bottles was also switched, to assure that the mice were not going repeatedly to one bottle simply out of habit. The mice lacking the D2 receptor shied away from the alcohol, while the normal mice showed a preference for it. There were no differences between the normal mice and mice lacking D2 receptors in their consumption of saccharine or quinine. The mice missing the D2 gene did show a lower sensitivity to alcohol, meaning they demonstrated less disturbance in balance and activity at identical blood alcohol levels.

The D2 receptor has been the subject of intense scrutiny. Some researchers have proposed that mutations in the D2 receptor gene in humans are one of the roots of alcoholism. The OHSU and VA research paints a more complex picture. "It says that the D2 receptor is in some way involved in the animal's choice to drink or not to drink," said David Grandy, Ph.D., associate professor of physiology and pharmacology at OHSU and a co-author of the paper. "But how the receptor relates to euphoria or abuse of the drug isn't yet clear. It will require extensive genetic screening of humans to determine which specific mutations in the D2 receptor gene may be connected with alcoholism. Our research doesn't point towards a single 'alcoholic' gene, but rather towards a complex interaction between several receptors and systems in the brain."

Further research will focus on measuring those interactions. Phillips and other OHSU and VA scientists have also found that mice without a receptor sensitive to serotonin, another substance connected with pleasure, drink more than mice that have the gene. Phillips, Grandy and others are now working on breeding mice that lack both the D2 and serotonin receptors.


Contact: Henry Sessions
Oregon Health & Science University

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