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

Brain Structure and Function - Tập 224 - Trang 2871-2882 - 2019
Goran Papenberg1, Lars Jonasson2,3, Nina Karalija2,4, Jarkko Johansson2,4, Ylva Köhncke, Alireza Salami1,2,3,5, Micael Andersson2,3, Jan Axelsson2,4, Anders Wåhlin2,4, Katrine Riklund2,4, Ulman Lindenberger6,7,8, Martin Lövdén1, Lars Nyberg2,3,4, Lars Bäckman1
1Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden
2Umeå center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden
3Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
4Department of Radiation Sciences, Umeå University, Umeå, Sweden
5Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
6Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
7Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany
8Max Planck UCL Centre for Computational Psychiatry and Ageing Research, London, UK

Tóm tắt

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.

Tài liệu tham khảo

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