Receptor variant influences dopamine response to alcohol

May 18, 2010

A genetic variant of a receptor in the brain's reward circuitry plays an important role in determining whether the neurotransmitter dopamine is released in the brain following alcohol intake, according to a study led by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health. Dopamine is involved in transmitting the euphoria and other positive subjective effects produced by alcohol.

A report of the findings, which help explain the diverse for alcohol use disorders, will appear online in on May 18, 2010.

"By advancing our understanding of the neurobiology that underlies the addictive properties of alcohol, this finding helps us understand why alcohol affects people in very different ways," says NIAAA Acting Director Kenneth R. Warren, Ph.D. "This kind of information also aids the development of personalized medications for alcohol problems."

Receptors for brain molecules known as opioid peptides help initiate the neurochemical reactions that underlie the positive effects produced by alcohol. Activation of the mu-subtype of opioid receptor following triggers the release of dopamine from the forebrain.

"But there is much variation in alcohol-induced responses that are thought to be related to dopamine," explains Markus Heilig, M.D., Ph.D., NIAAA clinical director and the study's senior author. "Previous studies by our group and others suggest that variants of opioid genes may contribute to the observed variation, possibly through effects on alcohol-induced dopamine release."

He notes, for example, that people who carry the mu-opioid receptor variant designated as 118G report increased euphoria following alcohol consumption. Dr. Heilig's group has reported that a similar mu-opioid receptor variant in monkeys heightened the stimulating effects of alcohol and increased their alcohol consumption.

In the current study, first author Vijay A. Ramchandani, Ph.D., an investigator in NIAAA's Laboratory of Clinical and Translational Studies, Dr. Heilig, and their colleagues explored whether the 118G mu-opioid receptor variant influences dopamine release from a forebrain region called the ventral striatum in response to alcohol.

Using human positron emission tomography (PET), an imaging technique that allowed the researchers to analyze dopamine activity in the brain, they compared dopamine release in two groups of people that had been given a dose of alcohol. The groups consisted of those who carried a copy of the gene for the 118G mu-opioid receptor variant, and those who carried only genes for the more common 118A variant. They found that only people with the 118G variant had a dopamine response to alcohol - no such response happened in subjects with the 118A receptor variant.

In a separate experiment, they inserted genes for the human 118G or 118A mu-opioid receptor variants into mice and then directly measured the animals' dopamine response to a dose of alcohol. Mice with the 118G variant showed a fourfold higher peak dopamine response to the alcohol challenge compared to mice with the 118A variant.

"Taken together, our data strongly support a causal role of the 118G variant of the mu-opioid receptor to confer a more vigorous dopamine response to alcohol in the ventral striatum," says Dr. Ramchandani. "The findings add further support to the notion that individuals who possess this receptor variant may experience enhanced pleasurable effects from alcohol that could increase their risk for developing and dependence. It may also explain why these individuals, once addicted, benefit more from treatment with blockers of endogenous opioids."

Explore further: In funk music, rhythmic complexity influences dancing desire

Provided by National Institutes of Health

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Scientists identify gene that influences alcohol consumption

Dec 05, 2007

A variant of a gene involved in communication among brain cells has a direct influence on alcohol consumption in mice, according to a new study by scientists supported by the National Institute on Alcohol Abuse and Alcoholism ...

Gene therapy reduces cocaine use in rats

Apr 16, 2008

Researchers at the U.S. Department of Energy's Brookhaven National Laboratory have shown that increasing the brain level of receptors for dopamine, a pleasure-related chemical, can reduce use of cocaine by 75 percent in rats ...

Brain stress system presents possible treatment

Feb 26, 2008

A brain circuit that underlies feelings of stress and anxiety shows promise as a new therapeutic target for alcoholism, according to new studies by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), ...

Recommended for you

Screenagers face troubling addictions from an early age

8 hours ago

In 1997, Douglas Rushkoff boldly predicted the emergence a new caste of tech-literate adolescents. He argued that the children of his day would soon blossom into "screenagers", endowed with effortless advantages over their parents, ...

Better memory at ideal temperature

8 hours ago

People's working memory functions better if they are working in an ambient temperature where they feel most comfortable. That is what Leiden psychologists Lorenza Colzato and Roberta Sellaro conclude after having conducted ...

User comments : 0

More news stories

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Researchers see hospitalization records as additional tool

Comparing hospitalization records with data reported to local boards of health presents a more accurate way to monitor how well communities track disease outbreaks, according to a paper published April 16 in the journal PLOS ON ...

Ebola virus in Africa outbreak is a new strain

The Ebola virus that has killed scores of people in Guinea this year is a new strain—evidence that the disease did not spread there from outbreaks in some other African nations, scientists report.