PET imaging of D2/3 receptors following acute dopamine depletion reveals a lower level of endogenous dopamine in cocaine dependence

Objectives Previous PET imaging studies have demonstrated that cocaine dependence is associated with a decrease in dopamine D2/3 receptor binding compared to healthy controls. 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. Thus, the goal of this study was to measure D2/3 receptors following dopamine depletion in cocaine dependent volunteers compared to healthy controls.

Methods Fifteen each of cocaine dependent participants and healthy controls underwent scans with [11C]raclopride: under a baseline condition and an acute depletion of endogenous dopamine using alpha-methyl-para-tyrosine (AMPT). 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 Cocaine dependence was associated with lower levels of endogenous dopamine compared to control subjects, measured as an increase in [11C]raclopride binding following AMPT administration. The increase in [11C]raclopride binding in the striatum was 12.7 ± 5.5% for healthy controls and 6.7 ± 6.4% for cocaine dependent volunteers.

Conclusions Cocaine dependence is associated with both a decrease in D2/3 receptor binding potential and a decrease in the levels of endogenous dopamine compared to matched control subjects.