Predisposition to alcoholism is likely an interaction between genetic and environmental factors that confer vulnerability and protection. Alcoholic subjects have low levels of dopamine D2 receptors in striatum, and increasing D2 receptor levels in laboratory animals reduces alcohol consumption.
To test whether high levels of D2 receptors may be protective against alcoholism and whether this is mediated by their modulation of activity in orbitofrontal cortex and cingulate gyrus (regions involved in salience attribution, emotional reactivity, and inhibitory control).
Research (nonalcoholic subjects with a family history of alcoholism) and comparison (nonalcoholic subjects with a negative family history) sample.
Fifteen nonalcoholic subjects who had an alcoholic father and at least 2 other first- or second-degree relatives who were alcoholics (family-positive group) and 16 nonalcoholic controls with no family history of alcoholism (family-negative group).
Main Outcome Measures
Results of positron emission tomography with raclopride C 11 to assess D2 receptors and with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain function). Personality measures were obtained with the Multidimensional Personality Questionnaire.
Availability of D2 receptors was significantly higher in caudate and ventral striatum in family-positive than family-negative subjects. In family-positive but not family-negative subjects, striatal D2 receptors were associated with metabolism in anterior cingulate (Brodmann area 24/25) and orbitofrontal (Brodmann area 11) and prefrontal (Brodmann area 9/10) cortices, and with personality scores of positive emotionality.
The higher-than-normal D2 receptor availability in nonalcoholic members of alcoholic families supports the hypothesis that high levels of D2 receptors may protect against alcoholism. The significant associations between D2 receptors and metabolism in frontal regions involved with emotional reactivity and executive control suggest that high levels of D2 receptors could protect against alcoholism by regulating circuits involved in inhibiting behavioral responses and in controlling emotions.