Lower level of endogenous dopamine in patients with cocaine dependence: findings from PET imaging of D(2)/D(3) receptors following acute dopamine depletion.
OBJECTIVE
Previous positron emission tomography (PET) imaging studies have demonstrated that cocaine dependence is associated with a decrease in dopamine type 2 and 3 (D(2)/D(3)) receptor binding in cocaine-dependent individuals relative to healthy comparison subjects. However, given the nature of PET imaging, it is possible that the measured decrease in radiotracer binding results from an increase in baseline dopamine levels. The purpose of this study was to measure D(2)/D(3) receptors following acute dopamine depletion in cocaine-dependent volunteers relative to healthy comparison subjects.


METHODS
Cocaine-dependent volunteers (N=15) and healthy matched comparison subjects (N=15) were scanned using PET, with the dopamine receptor radiotracer [(11)C]raclopride, at baseline and again following acute depletion of endogenous dopamine via alpha-methyl-para-tyrosine (AMPT) administration. Changes in radiotracer binding were measured in the subdivisions of the striatum (caudate, putamen, and ventral striatum) in addition to the striatum as a whole.


RESULTS
Findings revealed that cocaine-dependent volunteers exhibited lower levels of endogenous dopamine relative to comparison subjects, which was measured as an increase in [(11)C]raclopride binding following AMPT administration. The increase in [(11)C]raclopride binding in the striatum was 11.1% (SD=4.4%) in healthy comparison subjects and 5.7% (SD=5.9%) in cocaine-dependent volunteers. Similar differences were seen in the subdivisions of the striatum.


CONCLUSIONS
The decrease in striatal D(2)/D(3 )receptors associated with cocaine dependence cannot be attributed to higher levels of endogenous dopamine.
Martinez
Diana
D
Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons, New York, USA. dm437@columbia.edu
Greene
Kaitlin
K
Broft
Allegra
A
Kumar
Dileep
D
Liu
Fei
F
Narendran
Rajesh
R
Slifstein
Mark
M
Van Heertum
Ronald
R
Kleber
Herbert D
HD
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D019805:alpha-Methyltyrosine; D004298:Dopamine