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 [11C]raclopride (1 at baseline, 1 with an i.v. 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 (deltaBP, 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 D2/D3 receptor availability between the conditions. Data from the striatal deltaBP 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.
Yoder
Karmen K
KK
Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana, USA. kkyoder@iupui.edu
Constantinescu
Cristian C
CC
Kareken
David A
DA
Normandin
Marc D
MD
Cheng
Tee-Ean
TE
O'Connor
Sean J
SJ
Morris
Evan D
ED
D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000378:metabolism* / Q000523:psychology; D001479:Basal Ganglia / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D049268:Positron-Emission Tomography
D004298:Dopamine