Increasing dopamine D2 receptors may be a key to effective treatment.
A new study suggests that differences in the chemical messengers within the brain's reward circuits may explain why some people with a strong family history of alcoholism also become dependent, while others don't.
A team of scientists working at the Brookhaven National Laboratory in Upton, N.Y., have found that elevated levels of brain cell receptors called D2 for dopamine -- a chemical messenger in the reward circuits -- may provide a protective effect for those most at risk for developing alcoholism. The D2 receptor is one of five subtypes of dopamine receptors.
"Higher levels of dopamine D2 receptors may provide protection against alcoholism by triggering the brain circuits involved in inhibiting behavioral responses to the presence of alcohol," said the study's lead author, Dr. Nora Volkow, director of the National Institute on Drug Abuse and former associate laboratory director for life sciences at Brookhaven, a Department of Energy lab.
"This means that treatment strategies for alcoholism that increase dopamine D2 receptors could be beneficial for at-risk individuals," she added.
The findings were reported Monday in the Archives of General Psychiatry's September issue.
Earlier research at Brookhaven had showed that increasing dopamine D2 receptors by genetic manipulation had the effect of lowered alcohol consumption by rats that had been trained or were genetically predisposed to drink large quantities of alcohol.
Another study found that such D2 receptor gene therapy reduced drinking in mice with normal to somewhat low levels of the receptors before.
For the new study, researchers compared the number of D2 receptors in two groups of human subjects -- 16 nonalcoholic individuals with no family history of alcoholism and 15 nonalcoholic individuals with a family history of alcoholism.
That was defined as having a biological father with early onset alcoholism and at least two other first or second-degree relatives (parent, child, sibling, grandparent, grandchild, cousin, aunt or uncle) with alcoholism.
The researchers studied high-risk individuals rather than people diagnosed with drinking disorders because chronic alcohol abuse reduces the number of dopamine receptors over time, making comparisons difficult.
Both groups of participants were scanned with positron emission tomography (PET) and were given two radioactive tracers to assess their dopamine D2 receptor levels and brain glucose, a marker of brain function.
The scans showed high levels of D2 receptors in the brains of participants with a family history of alcoholism, particularly in the frontal regions of the brain associated with emotional reactions to stress and cognitive control of decisions about drinking.
Those with a family history of alcoholism had receptor levels an average of 10 percent higher than in the brains of those with no family history of alcoholism.
"This suggests that dopamine D2 receptors in these brain regions protect high-risk individuals from becoming alcoholic," said Dr. Gene-Jack Wang, chairman of the lab's medical department and principal investigator for the study.
"This protective effect may combine with emotional and environmental factors to compensate for higher inherited vulnerability."
Each of the study participants was also given a personality test to measure his or her tendency to be an extrovert or introvert, also known as positive or negative emotionality. Positive emotionality is believed to decrease the likelihood of alcohol abuse.
"We found that individuals who had the highest level of dopamine D2 receptors were those who were extroverted and more motivated by positive rewards," Volkow said.
"This held true for both individuals with and without a family history of alcoholism."