Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain

• Published in: Neurobiology of aging 2000-09, Vol.21 (5), p.683-688
• Main Authors: Kaasinen, Valtteri, Vilkman, Harry, Hietala, Jarmo, Någren, Kjell, Helenius, Hans, Olsson, Hans, Farde, Lars, Rinne, Juha O.
• Format: Article
• Language: English
• Subjects: [ 11C]FLB 457; Adult; Aged; Aging; Aging - metabolism; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Development. Senescence. Regeneration. Transplantation; Dopamine Antagonists; Dopamine D2-like receptors; Extrastriatal; Frontal Lobe - diagnostic imaging; Frontal Lobe - metabolism; Fundamental and applied biological sciences. Psychology; Gyrus Cinguli - diagnostic imaging; Gyrus Cinguli - metabolism; Hippocampus - diagnostic imaging; Hippocampus - metabolism; Humans; Male; Middle Aged; Pyrrolidines; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3; Salicylamides; Temporal Lobe - diagnostic imaging; Temporal Lobe - metabolism; Thalamus - diagnostic imaging; Thalamus - metabolism; Tomography, Emission-Computed, Single-Photon; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(00)00149-4

Loss of dopamine D2-like receptors in the striatum has been associated with both normal human aging and impairment of cognitive and motor functions in the elderly. To investigate whether there are age-associated changes in dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the striatum, a D2/3R selective high-affinity radioligand [ 11C]FLB 457 was used in positron emission tomography (PET) examinations for 24 normal healthy male subjects (age range 19–74 years). Significant age-related declines of D2/3Rs were detected in all the brain regions studied: the anterior cingulate cortex (decline of 13% per increase of a decade in age, P < 0.001), the frontal cortex (11%, P < 0.001), the lateral temporal cortex (10%, P < 0.001), the hippocampus (10%, P < 0.01), the medial temporal cortex (9%, P < 0.001), the amygdala (7%, P < 0.01), the medial thalamus (6%, P < 0.001) and the lateral thalamus (5%, P < 0.01). The rate of D2/3R decline was significantly faster in the frontal cortex as compared to the medial temporal cortex ( P < 0.05, Bonferroni corrected) and as compared to the medial thalamus ( P < 0.05, Bonferroni corrected). These results indicate that the previously demonstrated age-related decline in striatal dopamine D2 receptors extends to several extrastriatal regions in normal human males. Further, the rate of D2/3R decline may be faster in the frontal cortex as compared to the temporal and thalamic regions.