Mapping the landscape of human dopamine D2/3 receptors with [11C]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 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.
['Papenberg|Goran|G|http://orcid.org/0000-0003-0279-1988', 'Jonasson|Lars|L|', 'Karalija|Nina|N|', 'Johansson|Jarkko|J|', 'Köhncke|Ylva|Y|', 'Salami|Alireza|A|', 'Andersson|Micael|M|', 'Axelsson|Jan|J|', 'Wåhlin|Anders|A|', 'Riklund|Katrine|K|', 'Lindenberger|Ulman|U|', 'Lövdén|Martin|M|', 'Nyberg|Lars|L|', 'Bäckman|Lars|L|']
D000368:Aged D001921:Brain D003342:Corpus Striatum D005260:Female D006801:Humans D008032:Limbic System D008297:Male D008875:Middle Aged D020891:Raclopride D017448:Receptors, Dopamine D2 D050637:Receptors, Dopamine D3
Dopamine D2/3 receptors [11C]raclopride COBRA study Inter-individual differences Structural-equation modeling