Mapping the landscape of human dopamine D2/3 receptors with [(11)C]raclopride

The dopamine D2/3 system is fundamental for sensory, motor, emotional, and cognitive aspects of behavior. Small-scale human histopathological and animal studies show high density of D2/3 dopamine receptors (D2/3DR) in striatum, but also demonstrate the existence of such receptors across cortical and limbic regions. Assessment of D2/3DR BP(ND) in the extrastriatal regions with [(11)C]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum. We describe the distribution and interregional links of D2/3DR availability measured with PET and [(11)C]raclopride across the human brain in a large sample (N = 176; age range 64–68 years). Structural equation modeling revealed that D2/3DR availability can be organized according to anatomical (nigrostriatal, mesolimbic, mesocortical) and functional (limbic, associative, sensorimotor) dopamine pathways. D2/3DR availability in corticolimbic functional subdivisions showed differential associations to corresponding striatal subdivisions, extending animal and pharmacological work. Our findings provide evidence on the dimensionality and organization of [(11)C]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00429-019-01938-1) contains supplementary material, which is available to authorized users.