Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum.
BACKGROUND
A decrease in dopamine type 2 receptors (D2) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D2 receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [11C]raclopride.


METHODS
Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challenge (amphetamine .3 mg/kg intravenous). The outcome measures for baseline D2 receptor availability were binding potential (BP) and the equilibrium partition coefficient (V3''). Amphetamine-induced [11C]raclopride displacement was measured as the difference in V3'' between the two scans.


RESULTS
[11C]raclopride BP was significantly reduced by 16.6% in the limbic striatum, 19.2% in the associative striatum, and 21.3% in the sensorimotor striatum in AD subjects compared with HC. The alcohol-dependent subjects showed a blunting of amphetamine-induced dopamine release in the limbic striatum: [11C]raclopride displacement was -5.2% +/- 3.6% in AD subjects compared with -13.0% +/- 8.8% in HC. However, no significant difference in [11C]raclopride displacement was seen in the associative (-4.6% +/- 5.8% in AD subjects vs. -6.7 +/- 5.4% in HC) and sensorimotor (-12.3% +/- 7.3% in AD subjects vs. -13.7 +/- 7.5% in HC) subdivisions of the striatum between the two groups.


CONCLUSIONS
Alcohol dependence was associated with a decrease in D2 receptors in each striatal subdivision, whereas amphetamine-induced dopamine release was reduced in the limbic striatum only.
Martinez
Diana
D
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. dm437@columbia.edu
Gil
Roberto
R
Slifstein
Mark
M
Hwang
Dah-Ren
DR
Huang
Yiyun
Y
Perez
Audrey
A
Kegeles
Lawrence
L
Talbot
Peter
P
Evans
Suzette
S
Krystal
John
J
Laruelle
Marc
M
Abi-Dargham
Anissa
A
D000328:Adult; D000437:Alcoholism / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D002250:Carbon Radioisotopes; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D049268:Positron-Emission Tomography; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002250:Carbon Radioisotopes; D017448:Receptors, Dopamine D2; D020891:Raclopride; D003913:Dextroamphetamine; D004298:Dopamine