Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine.
The goal of this study was to determine D(1) receptor availability in human cocaine-dependent (CD) subjects and matched healthy controls (HCs). In addition, the CD subjects performed cocaine self-administration sessions in order to explore the association between D(1) receptor availability and cocaine-seeking behavior. Twenty-five CD subjects (40+/-4 years, 19M/6 F) and 23 matched HCs (38+/-4 years, 19M/4F) were scanned with PET and the radiotracer [(11)C]NNC 112. During the cocaine self-administration sessions, CD volunteers were given the choice to self-administer cocaine (0, 6, and 12 mg) or to receive a monetary voucher worth $5. D(1) receptor availability was measured in the limbic, associative, and sensori-motor striatum in addition to cortical brain regions. No difference in D(1) receptor availability was seen between the two groups. A negative association was seen between D(1) receptor BP(ND) in the limbic striatum and the choice for the 6 mg dose of cocaine (r=-0.47, p=0.02, corrected for age). These results do not support the hypothesis that cocaine dependence is associated with a reduction in D(1) receptor availability in the striatum. However, within the CD subjects, low D(1) receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D(1) receptor availability may be associated with an increased risk of relapse in cocaine dependence.
Martinez
Diana
D
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Slifstein
Mark
M
Narendran
Rajesh
R
Foltin
Richard W
RW
Broft
Allegra
A
Hwang
Dah-Ren
DR
Perez
Audrey
A
Abi-Dargham
Anissa
A
Fischman
Marian W
MW
Kleber
Herbert D
HD
Laruelle
Marc
M
D000328:Adult; D001552:Benzazepines / Q000378:metabolism; D001572:Benzofurans / Q000378:metabolism; D001931:Brain Mapping; D002755:Choice Behavior / Q000502:physiology*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012055:Reinforcement Schedule; D012646:Self Administration / Q000379:methods
D001552:Benzazepines; D001572:Benzofurans; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; C077123:NNC 112; D003042:Cocaine