Abstract
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 BPND in the extrastriatal regions with [11C]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 [11C]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 [11C]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways.
Highlights
Positron emission tomography (PET) can be used to quantify dopamine (DA) receptors in the human brain, using radioligands that bind selectively to the receptors of interest. [ 11C]Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.1 3 Vol.:(0123456789)Brain Structure and Function (2019) 224:2871–2882Assessment of D2/3 dopamine receptors (D2/3DR) BPND in extrastriatal regions with [11C]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum (Hall et al 1994; Farde et al 1988)
We describe the ”landscape” of [ 11C]raclopride BPND in the human brain and investigate whether D2/3DR availability is organized according to anatomical and functional dopamine pathways, which would support the validity of extrastriatal [11C]raclopride measurements
Between-person differences in D2/3DR availability measured with [11C]raclopride could be accounted for by an anatomical model as shown previously with the highaffinity ligand [18F]fallypride (Zald et al 2010)
Summary
A more recent study reported high ICCs across 7 months for [11C]raclopride BPND in both striatal and extrastriatal brain regions (n = 27; ICCs > 0.9 for frontal and temporal cortex; Karalija et al 2019). This suggests that extrastriatal [ 11C]raclopride BPND values represent a true signal rather than mere noise. We describe the ”landscape” of [ 11C]raclopride BPND in the human brain and investigate whether D2/3DR availability is organized according to anatomical and functional dopamine pathways, which would support the validity of extrastriatal [11C]raclopride measurements
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