Response to alcohol depends on genes

20 Oct 2010

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Many studies have suggested that genetic differences make some individuals more susceptible to the addictive effects of alcohol and other drugs. Now scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory provide the first experimental evidence to directly support this idea in a study in mice reported in the October 19, 2010, issue of Alcoholism Clinical Experimental Research.

Levels of CB1 receptors in mice as measured by autoradiography, shown using a rainbow scale with blue representing the lowest levels and red the highest. Mice with no dopamine receptors drinking water (B) had higher levels of CB1 receptors than normal mice drinking water (A). Drinking alcohol seemed to negate this ''up-regulation'' in the dopamine-receptor-deficient mice (D), which had about half the level of CB1 receptors compared to the dopamine-receptor-deficient water drinkers (B).Click on the image to download a high-resolution version.Levels of CB1 receptors in mice as measured by autoradiography, shown using a rainbow scale with blue representing the lowest levels and red the highest.

Mice with no dopamine receptors drinking water (B) had higher levels of CB1 receptors than normal mice drinking water (A). Drinking alcohol seemed to negate this ''up-regulation'' in the dopamine-receptor-deficient mice (D), which had about half the level of CB1 receptors compared to the dopamine-receptor-deficient water drinkers (B).

The study compared the brain's response to long-term alcohol drinking in two genetic variants of mice. One strain lacked the gene for a specific brain receptor known as dopamine D2, which responds to dopamine, the brain's ''feel good'' chemical, to produce feelings of pleasure and reward.

The other strain was genetically normal. In the dopamine-receptor-deficient mice (but not the genetically normal strain), long-term alcohol drinking resulted in significant biochemical changes in areas of the brain well know to be involved in alcoholism and addiction.

''This study shows that the effects of chronic alcohol consumption on brain chemistry are critically influenced by an individual's pre-existing genetic makeup,'' said lead author Panayotis (Peter) Thanos, a neuroscientist with Brookhaven Lab and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging.

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