This year’s Nobel Prize in physiology or medicine was awarded to three scientists for discovering principles that allow the modification of a mouse’s genes by the use of embryonic stem cells. This is a reminder of the importance of mice in addiction research. “Knockout mice” were created in the 1980’s; these mice were missing one or more specific genes responsible for various diseases, which enabled scientists to develop research techniques and treatment protocols for human diseases. This is possible because 95% of a mouse’s genetics match that of human beings. To date, more than 500 mouse models of human ailments, including those affecting diabetes, cancer, and cystic fibrosis, along with diseases affecting the cardiovascular and central nervous systems, have been developed.
Knockout mice were available before the 80’s, but they were bred by accident. In the late 60s early 70s, Gerald Mclearen of the University of Colorado successfully isolated a strain of mice that hated alcohol and another that loved alcohol. Researchers used these mice to study the effects of stress, nutrition, and the use of alcohol on the development of alcoholism.
Experiments showed that mice genetically bred to prefer alcohol over water would drink alcohol to excess. Even 150-proof alcohol was preferred to water. The mice would drink until they killed themselves. Other experiments subjected genetically sober, alcohol hating mice to stress which mimicked human environments where violence, abuse, fear, and stress are common. The genetically sober mice came to prefer alcohol after days of this stress, probably because it relieved their anxiety and pain. These once sober mice consumed more and more alcohol and many died.
When researchers subtracted key essential amino acid and several types of B vitamins from the diet of another group of mice, those mice came to prefer alcohol to water. Finally, they force fed alcohol to sober mice who then continued to drink on their own and became alcoholic. Due to various combinations of heredity, environment, and psychoactive drugs, all the mice studied became alcoholics. When their brains were examined, the changes wrought by stress, nutrition, heredity, and by force-feeding alcohol were extremely similar.
These experiments, along with the knowledge that genetic manipulation can alter one’s susceptibility to alcohol abuse, led researchers Ernest Nobel at the University of California in Los Angeles and Kenny Blum at the University of Texas, San Antonio, to discover a gene (DRD2A1 allelle) that is more prevalent in alcoholics than in the general public (75% vs. less than 25%).
For more information on the Nobel Prize winners and a more extensive discussion of their discovery go to the official Nobel Prize site at http://nobelprize.org/nobel_prizes/medicine/laureates/2007/press.html