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Genetic Variant Plays Important Role in Brain’s Response to Alcohol

When people drink alcohol and feel euphoric, the neurotransmitter dopamine has been released in the brain, affecting the individual’s mood. But alcohol affects some people differently than others, so researchers at the National Institutes on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, set out to find the reasons why.

In a new study, the researchers found that a genetic variant of a receptor in the brain’s reward circuitry, which is responsible for the individual effects of alcohol consumption, influences the response of dopamine to alcohol. The report was published online in Molecular Psychiatry on May 18, 2010.

Kenneth R. Warren, Ph.D., acting director of NIAAA, said that by deepening the understanding of the underlying neurobiology of addiction, we can understand more about how and why alcohol affects people differently. This can also help in the creation of medications for alcohol addiction.

Receptors for brain molecules known as opioid peptides help catalyze the euphoric reactions to alcohol. In people who carry a mu-subtype of the opioid receptor, alcohol consumption releases dopamine into the brain. But alcohol-induced responses that are thought to be related to dopamine are so varied, according to Markus Heilig, M.D., Ph.D., the study’s lead author and clinical director of the NIAAA.

Dr. Heilig said that prior studies have suggests that variant genes may contribute to the varied response people have to alcohol, which could be due to the dopamine that is released after alcohol consumption. For example, people with the mu-opioid receptor variant reported increased euphoria after drinking alcohol. A similar genetic variant in monkeys heightened the euphoric effects of alcohol in monkeys, increasing their alcohol consumption.

Dr. Heilig, first author Vijay A. Ramchandani, Ph.D., an investigator in NIAAA's Laboratory of Clinical and Translational Studies, and colleagues used human positron emission tomography (PET), which allows researchers to analyze dopamine activity in the brain, to compare dopamine responses in two different groups of people who had been given alcohol: those who carried the mu-opioid receptor variant and those who did not. They found that only people with the variant had a dopamine response to alcohol consumption.

They also inserted genes for the variant receptor into mice and measured their dopamine response to alcohol, finding that mice with the variant released four times more dopamine compared to mice without the variant.

Dr. Ramchandani said that this strongly supports a casual role of the variant gene, which means that people with this receptor variant may be at a higher risk of abusing and becoming addicted to alcohol. This might also explain why people who are dependent on alcohol can benefit from medications that block the opioid receptors in the brain.

Source: Science Daily, Receptor Variant Influences Dopamine Response to Alcohol, May 18, 2010.

Posted on May 17th, 2010

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