Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

Abstract

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [(11)C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

Figure 1

Localization (left) and scatterplot (right) of the correlations between (A) caudate DA D2 receptor availability (as seed value) and thalamic (cluster maxima at x=9, y=−11, z=14) BOLD fMRI response and between (B) ventral striatum DA D2 receptor availability (as seed value) and medial prefrontal cortex (cluster maxima at x=0, y=43, z=39) BOLD fMRI response to monetary reward (45¢) in seven cocaine addicted individuals. Statistical threshold: p<.05 cluster-level corrected (minimum Z=2.5 or T=4.03). Minimum cluster size: 5 contiguous voxels (135 mm³). For display purposes, threshold was set at p<0.01 uncorrected.