Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving.
In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [(11)C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.
Wong
Dean F
DF
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0807, USA. dfwong@jhmi.edu
Kuwabara
Hiroto
H
Schretlen
David J
DJ
Bonson
Katherine R
KR
Zhou
Yun
Y
Nandi
Ayon
A
Brasić
James R
JR
Kimes
Alane S
AS
Maris
Marika A
MA
Kumar
Anil
A
Contoreggi
Carlo
C
Links
Jonathan
J
Ernst
Monique
M
Rousset
Olivier
O
Zukin
Stephen
S
Grace
Anthony A
AA
Lee
Jae Sung
JS
Rohde
Charles
C
Jasinski
Donald R
DR
Gjedde
Albert
A
London
Edythe D
ED
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D005260:Female; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D020891:Raclopride; D003042:Cocaine; D004298:Dopamine