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 [C-11]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 BPND 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. Neuropsychopharmacology (2009) 34, 1774-1782; doi:10.1038/npp.2008.235; published online 28 January 2009