Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving.
OBJECTIVE
Alcohol and other drugs of abuse stimulate dopamine release in the ventral striatum, which includes the nucleus accumbens, a core region of the brain reward system, and reinforce substance intake. Chronic alcohol intake is associated with down-regulation of central dopamine D(2) receptors, and delayed recovery of D(2) receptor sensitivity after detoxification is positively correlated with high risk for relapse. Prolonged D(2) receptor dysfunction in the ventral striatum may interfere with a dopamine-dependent error detection signal and bias the brain reward system toward excessive attribution of incentive salience to alcohol-associated stimuli.


METHODS
Multimodal imaging, with the radioligand [(18)F]desmethoxyfallypride and positron emission tomography as well as functional magnetic resonance imaging (fMRI), was used to compare 11 detoxified male alcoholics with 13 healthy men. The authors measured the association of D(2)-like dopamine receptors in the ventral striatum with alcohol craving and central processing of alcohol cues.


RESULTS
Activation of the medial prefrontal cortex and striatum by alcohol-associated stimuli, relative to activation by neutral visual stimuli, was greater in the detoxified alcoholics than in the healthy men. The alcoholics displayed less availability of D(2)-like receptors in the ventral striatum, which was associated with alcohol craving severity and with greater cue-induced activation of the medial prefrontal cortex and anterior cingulate as assessed with fMRI.


CONCLUSIONS
In alcoholics, dopaminergic dysfunction in the ventral striatum may attribute incentive salience to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive activation of neural networks associated with attention and behavior control.
Heinz
Andreas
A
Department of Psychiatry, Charité, Campus Mitte, Berlin, Germany.
Siessmeier
Thomas
T
Wrase
Jana
J
Hermann
Derik
D
Klein
Sabine
S
Grüsser
Sabine M
SM
Grüsser-Sinopoli
Sabine M
SM
Flor
Herta
H
Braus
Dieter F
DF
Buchholz
Hans Georg
HG
Gründer
Gerhard
G
Schreckenberger
Mathias
M
Smolka
Michael N
MN
Rösch
Frank
F
Mann
Karl
K
Bartenstein
Peter
P
D000328:Adult; D000428:Alcohol Drinking / Q000503:physiopathology / Q000523:psychology*; D000437:Alcoholism / Q000523:psychology* / Q000534:rehabilitation; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D016739:Behavior, Addictive / Q000000981:diagnostic imaging / Q000523:psychology*; D003463:Cues; D000431:Ethanol / Q000494:pharmacology*; D005462:Fluorine Radioisotopes; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D012457:Salicylamides; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data
D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C100958:desmethoxyfallypride; D000431:Ethanol