Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine.
OBJECTIVE
Dopamine is an important mediator of the reinforcing effects of cocaine, and alterations in dopamine function might be involved in cocaine dependence. The goals of the present study were to characterize pre- and postsynaptic dopamine function in recently detoxified cocaine-dependent subjects. Specifically, dopamine response to an acute amphetamine challenge was assessed in striatal subregions in cocaine-dependent and healthy comparison participants using positron emission tomography (PET). Furthermore, the relationship between this dopamine response and the choice to self-administer cocaine in a laboratory model of relapse was investigated.


METHODS
Twenty-four cocaine-dependent participants and 24 matched healthy subjects underwent [(11)C]raclopride scans under a baseline condition and following intravenous amphetamine administration (0.3 mg/kg). Cocaine-dependent participants also completed cocaine self-administration sessions in which a priming dose of cocaine was followed by the choice to either self-administer subsequent cocaine doses or receive a monetary reward.


RESULTS
Cocaine dependence was associated with a marked reduction in amphetamine-induced dopamine release in each of the functional subregions of the striatum (limbic striatum: -1.2% in cocaine-dependent participants versus -12.4% in healthy subjects; associative striatum: -2.6% versus -6.7%, respectively; sensorimotor striatum: -4.3% versus -14.1%). Blunted dopamine transmission in the ventral striatum and anterior caudate was predictive of the choice for cocaine over money.


CONCLUSIONS
Cocaine dependence is associated with impairment of dopamine function, and this impairment appears to play a critical role in relapse.
Martinez
Diana
D
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. dm437@columbia.edu
Narendran
Rajesh
R
Foltin
Richard W
RW
Slifstein
Mark
M
Hwang
Dah-Ren
DR
Broft
Allegra
A
Huang
Yiyun
Y
Cooper
Thomas B
TB
Fischman
Marian W
MW
Kleber
Herbert D
HD
Laruelle
Marc
M
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000503:physiopathology; D002250:Carbon Radioisotopes; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006801:Humans; D008032:Limbic System / Q000503:physiopathology; D008297:Male; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D020891:Raclopride; D012054:Reinforcement, Psychology; D012646:Self Administration
D002250:Carbon Radioisotopes; D020891:Raclopride; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine