For the first time, animal research clearly demonstrates that a brain element known to produce pleasure, the D2 dopamine receptor, plays a critical role in alcohol consumption. "These results are important because they provide a reason for renewed interest in developing treatments that involve D2 dopamine receptors for alcoholism," says lead author of the study, Tamara Phillips, PhD, of Oregon Health Sciences University and the Department of Veterans Affairs Medical Center in Portland. "If a drug could be developed that specifically blocks these receptors without having adverse side-effects, it might hold promise for reducing alcohol drinking."
Phillips' study, funded by the Department of Veterans Affairs, the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse, is published in the November issue of Nature Neuroscience.
"It has been very difficult to characterize the mechanisms that make alcohol habit-forming, but this study adds significantly to the accumulating evidence that has suggested a role for the dopamine systems, already known to play a role in habit-forming properties of heroin and cocaine," says Roy Wise, PhD, an addiction expert at the National Institute on Drug Abuse. "The finding is important because it shows that there are some important similarities between the mechanisms of addictions for different drugs."
The idea that the brain chemical dopamine and its receptors, the receiving areas where it carries out its actions, are involved in alcohol addiction has been controversial. For example, early reports suggested that people carrying one form of the dopamine D2 receptor gene were at higher risk for the development of alcoholism than were individuals carrying a different form of the gene. Other studies did not confirm this finding. "Our results, however, clearly suggest that the dopamine D2 receptor plays a critical role in determining how much alcohol a mouse will drink," says Phillips.
In the study, the researchers found that mice bred without D2 dopamine receptors voluntarily drank about half as much alcohol as did their normal littermates when they were given a choice of alcohol or tap water. "The altered mice actually show an aversion for alcohol, whereas their normal littermates show a preference," says Phillips. The researchers also found that the altered mice show a reduced sensitivity to alcohol. "The normal littermates show reduced locomotion following an injection of alcohol while the locomotion of the mutant mice did not change," says Phillips. "In addition, the normal littermates show increased stumbling and the mutant mice show this effect to a much smaller degree."
In future studies, the scientists plan to determine if the altered animals' dip in drinking is due to a loss of pleasure, since dopamine is a major component of the brain's reward pathways.
