Linking a genetic variant to alcoholism

2013

Challenge

Alcoholism has a moderate to high heritability, but genetic variations that contribute to alcoholism have been difficult to identify, partly because many are uncommon.

Advance

IRP researchers led by David Goldman, M.D., and Markus Heilig, M.D., Ph.D., found that a specific glutamate receptor plays a role in alcohol-seeking in rats. They showed that animals with a naturally occurring truncated version of that receptor gene preferred alcohol more than wild-type, outbred animals. Experiments to pharmacologically block the receptor in wild-type animals led to an increase in alcohol consumption, as did experiments to completely knock out the gene, suggesting that this receptor plays a pivotal role in alcohol preference.

Impact

The discovery of this genetic variant within an alcohol-preferring rat strain—the standard animal model of alcoholism—clearly illuminates one mechanism involved in alcohol abuse and provides an important step in the scientific path to understanding causation of alcoholism.

Publications

Zhou Z, Karlsson C, Liang T, Xiong W, Kimura M, Tapocik JD, Yuan Q, Barbier E, Feng A, Flanigan M, Augier E, Enoch MA, Hodgkinson CA, Shen PH, Lovinger DM, Edenberg HJ, Heilig M, Goldman D. (2013). Loss of metabotropic glutamate receptor 2 escalates alcohol consumption. Proc Natl Acad Sci U S A. 110(42), 16963-8.