Dopamine D₃ receptor alterations in cocaine-dependent humans imaged with [¹¹C](+)PHNO.
BACKGROUND
Evidence from animal models and postmortem human studies points to the importance of the dopamine D₃ receptor (D₃R) in cocaine dependence (CD). The objective of this pilot study was to use the D₃R-preferring radioligand [(11)C](+)PHNO to compare receptor availability in groups with and without CD.


METHODS
Ten medically healthy, non-treatment seeking CD subjects (mean age 41 ± 8) in early abstinence were compared to 10 healthy control (HC) subjects (mean age 41 ± 6) with no history of cocaine or illicit substance abuse. Binding potential (BPND), a measure of available receptors, was determined with parametric images, computed using the simplified reference tissue model (SRTM2) with the cerebellum as the reference region.


RESULTS
BPND in CD subjects was higher in D₃R-rich areas including the substantia nigra ((SN) 29%; P=0.03), hypothalamus (28%; P=0.02) and amygdala (35%; P=0.03). No between-group differences were observed in the striatum or pallidum. BPND values in the SN (r=+0.83; P=0.008) and pallidum (r=+0.67; P=0.03) correlated with years of cocaine use.


CONCLUSIONS
Between-group differences suggest an important role for dopaminergic transmission in the SN, hypothalamus and amygdala in CD. Such findings also highlight the potential relevance of D₃R as a medication development target in CD.
Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Diagnostic Radiology, Yale University, New Haven, CT, USA. Electronic address: david.matuskey@yale.edu.
David
D
Matuskey
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Jean-Dominique
JD
Gallezot
Department of Psychiatry, Yale University, New Haven, CT, USA.
Brian
B
Pittman
Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Wendol
W
Williams
Department of Psychiatry, Yale University, New Haven, CT, USA.
Jane
J
Wanyiri
Department of Psychiatry, Yale University, New Haven, CT, USA.
Edward
E
Gaiser
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Dianne E
DE
Lee
Department of Psychiatry, Yale University, New Haven, CT, USA.
Jonas
J
Hannestad
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Keunpoong
K
Lim
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Minq-Qiang
MQ
Zheng
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Shu-fei
SF
Lin
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
David
D
Labaree
Department of Psychiatry, Yale University, New Haven, CT, USA.
Marc N
MN
Potenza
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Richard E
RE
Carson
Department of Psychiatry, Yale University, New Haven, CT, USA.
Robert T
RT
Malison
Department of Radiology and Psychiatry, New York University School of Medicine, New York, NY, USA.
Yu-Shin
YS
Ding
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005917:Globus Pallidus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D059906:Neuroimaging; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism
D010078:Oxazines; D050637:Receptors, Dopamine D3; C042631:naxagolide
Cocaine; D(3); Dopamine; Human; PET; [(11)C](+)PHNO