Researchers Hope Boosting Receptors Can Prevent Alcoholism

A number of brain chemicals have gotten bad press for causing alcoholism. At least 26 different genes may contribute to the illness (see article above left). But a large supply of at least one of these chemicals may help stave off the ailment in vulnerable individuals, according to a recent study.

That substance is the D₂ receptor—one of five receptors for the neurotransmitter dopamine. A scarcity of D₂ receptors has been noted in the brain's striatum region in alcoholic subjects. Other researchers have found that when rats genetically predisposed to heavy drinking had their D₂ receptors increased by genetic manipulation, they consumed less alcohol than normal. So Nora Volkow, M.D., director of the National Institute on Drug Abuse, with Colleagues at Brookhaven National Laboratory, the National Institute on Alcohol Abuse and Alcoholism, and the State University of New York Downstate, reasoned that while having too few D₂ receptors might predispose a person to alcoholism, having a larger supply of them might provide protection from the illness.

The scientists studied two groups of people to test this hypothesis. PET imaging was used to measure the number of dopamine D₂ receptors in the brains of 15 nonalcoholic subjects with a strong family history of alcoholism as well as the number of dopamine D₂ receptors in the brains of a control group of 16 nonalcoholic subjects with no family history of alcoholism. Both groups were comparable in age, gender, education, socioeconomic status, ethnicity, smoking histories, verbal IQ, and scores on the Beck Depression Inventory. The number of such receptors in the brains of the subjects with a family history of alcoholism was then compared with the number in the brains of the control subjects.

Significantly more D₂ receptors were found in the caudate and ventral striatum regions of the brains of those with a family history of alcoholism than in the caudate and ventral striatum regions of the brains of the control subjects. The caudate and ventral striatum are known to be involved in drinking decisions and reactions to emotional stress.

The level of D₂ receptors was only 10 percent higher on average in nonalcoholic subjects with a family history of alcoholism than it was in the control subjects, but that appears to make a big difference, the investigators noted in their report, which appeared in the September Archives of General Psychiatry.

“It is equivalent to what we have reported between subjects who show pleasant versus aversive responses to the stimulant drug methylphenidate,” they wrote. These results match data from a PET study of siblings discordant for cocaine abuse “that showed not only that the cocaine-abusing sibling had a lower D₂ receptor level than a control group, but also that the non-abusing sibling had a higher D₂ receptor level than the control group.”

Still to be determined is whether a generous endowment of D₂ receptors can shield people from alcoholism through their entire lives, the investigators added. Also to be determined, they granted, is how their findings might be deployed to treat or prevent alcoholism. One possible tack, Volkow noted in a press release issued by Brookhaven National Laboratory, might be finding a way to increase D₂ receptors in the brains of individuals at high risk of alcoholism.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism and the U.S. Department of Energy.

An abstract of “High Levels of Dopamine D₂ Receptors in Unaffected Members of Alcoholic Families” is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/63/9/999>.▪