Heterogeneous effects of alcohol on dopamine release in the striatum: A PET study

Background: A dopaminergic response to alcohol in humans has not been demonstrated consistently with positron emission tomography (PET). We hypothesized that the effect of alcohol on striatal dopamine (DA) release may be anatomically heterogeneous between subjects. Our approach was to identify voxels that exhibited alcohol-induced DA responses within the striatum, and to determine the relationships between DA responses and alcohol-related behavior. Methods: A novel method was developed to examine the anatomic extent and magnitude of striatal DA responses to alcohol across subjects. Thirteen healthy control subjects underwent 2 PET scans with [C-11]raclopride (1 at baseline, 1 with an IV alcohol infusion to a target breath alcohol concentration of either 60 or 80 mg%). Parametric images of striatal binding potential (BP) were used to create maps of change in BP (Delta BP, an index of changes in DA levels). The anatomic extent and magnitude of DA responses were determined with voxel extraction methods. Subjective responses (High, Intoxication) to the alcohol infusion and behavioral data from the 90-day time-line follow back were assessed for relationships with DA responses to alcohol. Results: A voxel-wise t-test between baseline and alcohol BP images did not show any differences in D-2/D-3 receptor availability between the conditions. Data from the striatal Delta BP maps nevertheless showed that the anatomic extent and magnitude of alcohol-induced DA release in the striatum are correlated with subjective responses to alcohol. Conclusions: The heterogeneity of dopaminergic responses to alcohol across subjects may be a reason for the lack of reports demonstrating DA involvement in alcohol-related behaviors. By allowing for different spatial patterns of DA release within each subject's striata, we showed correlations between alcohol-induced DA release in the striata and behavioral outcomes related to alcohol.