Amphetamine-Induced Dopamine Release: Markedly Blunted in Cocaine Dependence and Predictive of the Choice to Self-Administer Cocaine

Abstract

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. Method: 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.