Decreased binding of the D-3 dopamine receptor-preferring ligand [C-11]-()-PHNO in drug-nave Parkinsons disease

作者：Boileau Isabelle^*; Guttman Mark; Rusjan Pablo; Adams John R; Houle Sylvain; Tong Junchao; Hornykiewicz Oleh; Furukawa Yoshiaki; Wilson Alan A; Kapur Shitij; Kish Stephen J

来源：Brain, 2009, 132(5): 1366-1375.

DOI：10.1093/brain/awn337

• [C-11]raclopride
• [C-11]-()-PHNO
• Dopamine D-2/3 receptors
• Parkinsons disease
• positron emission tomography (PET)

The D-3 dopamine (DA) receptor is a member of the D-2-like DA receptor family. While the D-2 receptor is abundant especially in motor-regions of the striatum, the D-3 receptor shows a relative abundance in limbic regions and globus pallidus. This receptor is of current interest in neurology because of its potential involvement in psychiatric and motor complications in Parkinsons disease and the possibility that dopamine D-3-preferring agonist therapy might delay progression of the disorder. Preclinical data indicate that striatal levels of the D-3 (but not the D-2) DA receptor are decreased following lesion of nigrostriatal DA neurons; at present, there are no in vivo data on this receptor subtype in Parkinsons disease. The objective of this positron emission tomography study was to compare [C-11]-()-PHNO (D-3 versus D-2 preferring) and [C-11]raclopride (D-3 D-2) binding in brain of non-depressed, non-demented, dopaminergic drug-nave patients with early-stage Parkinsons disease (n 10), relative to matched-controls (n 9). Parkinsons disease was associated with a trend for bilaterally decreased [C-11]-()-PHNO (but not [C-11]raclopride) binding in the D-3-rich ventral striatum (11, P 0.07) and significantly decreased binding in globus pallidus (42, P 0.02). In contrast, in the primarily D-2-populated putamen, both [C-11]-()-PHNO (25, P 0.02) and [C-11]raclopride (25, P 0.01) binding were similarly increased, especially on the side contra-lateral to the symptoms. In the midbrain, presumably containing D-3 receptors localized to the substantia nigra, [C-11]-()-PHNO binding was normal. Decreased [C-11]-()-PHNO to [C-11]raclopride ratio correlated with motor deficits and lowered-mood (P 0.02). Our imaging data suggest that brain DA neuron loss in the human causes region-specific differential changes in DA D-2 and D-3 receptors with D-3 receptor downregulation possibly related to some motor and mood problems in Parkinson disease. D-3 receptor levels might be a determinant vulnerability factor underlying side-effects associated with treatment; hence, these initial findings provide valuable baseline information to understand the role of D-3 receptors in response to Parkinsons disease medication.

• 出版日期2009-5