March 19, 2007

A Brain Receptor's Role in Alcohol's Pleasure and Problems

A photo of a rhesus monkey

A new study in rhesus monkeys shows that a genetic variant of one component in the brain's reward circuitry heightens the stimulating effects of alcohol and leads the monkeys to drink more. The study extends previous research that suggests an important role for a similar variant in the development of human alcohol use disorders.

Molecules known as opioid peptides bind to opioid receptors in the brain to signal experiences of reward and reinforcement, as well as the euphoria and other positive effects produced by alcohol. Previous studies have shown that, among the brain’s various opioid receptors, the mu-subtype is most likely responsible for transmitting alcohol's positive effects. One variant called 118G has a greatly enhanced ability to bind opioid peptides. Recent studies have linked this variant with alcohol dependence in humans. People who have it also report increased euphoria when they drink alcohol.

Dr. Markus Heilig, Clinical Director of NIH's National Institute on Alcohol Abuse and Alcoholism (NIAAA), Dr. Christina Barr and their colleagues explored the link between genetic variants of mu-opioid receptors and alcohol-related behaviors in a group of 82 rhesus monkeys. Groups of monkeys had access to both alcoholic and non-alcoholic artificially sweetened solutions for one hour per day for a period of six weeks. The researchers measured the animals' alcohol intake and assessed their post-intake activity. They also tested which monkeys carried the gene for the mu-opioid receptor similar to the human 118G receptor.

The researchers reported in the March 2007 issue of Archives of General Psychiatry that, as they predicted, the monkeys with the variant similar to 118G showed increased activity following alcohol consumption. Males with the variant had a clear preference for the alcohol solution and drank an average of almost twice as much alcohol as other animals. Males with the variant also became intoxicated on almost 30% of testing days, while other animals did so on an average of only 8% of testing days.

“Although the pathway to alcoholism is influenced by many factors,” Heilig says, “our findings affirm that individuals who possess this receptor variant may experience enhanced pleasurable effects from alcohol that could increase their risk for developing alcohol abuse and dependence.”

Recent research suggests that medications designed to block opioid receptors are more effective in alcohol-dependent people with the gene for the 118G receptor. The current finding underscores the important role that the pleasurable and stimulating effects of alcohol play in the development of alcohol problems. This insight will also play a role in the development of future treatment strategies.

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