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Age differences in phosphodiesterase type‐IV and its functional response to dopamine D 1 receptor modulation in the living brain: A PET study in conscious monkeys
Author(s) -
Harada Norihiro,
Nishiyama Shingo,
Ohba Hiroyuki,
Sato Kengo,
Kakiuchi Takeharu,
Tsukada Hideo
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10067
Subject(s) - striatum , rolipram , dopamine , medicine , endocrinology , dopamine receptor d1 , phosphodiesterase , dopamine receptor , temporal cortex , chemistry , cerebellum , receptor , antagonist , neuroscience , psychology , biology , enzyme , biochemistry
The present study demonstrated the age‐related changes in the striatal dopamine D 1 receptor binding and its related cAMP second‐messenger system in the living brains of conscious young (6.4 ± 1.8 years old) and aged (19.5 ± 3.3 years old) monkeys ( Macaca mulatta ) using positron emission tomography (PET). For quantitative analysis of D 1 receptors, [ 11 C]SCH23390 was used and phosphodiesterase type‐IV (PDE‐IV) activity, as an index of cAMP system, was estimated by two scans with R ‐ and S ‐[ 11 C]rolipram. Significant age‐related decreases in D 1 receptor binding were observed in the striatum and frontal cortex. Analysis of uptake of R ‐ and S ‐[ 11 C]rolipram indicated age‐related decreases in PDE‐IV activity showing 22.0 and 25.2% decreases in the striatum and frontal cortex, respectively, while no significant changes were observed in the cerebellum. With systemic preadministration of the dopamine D 1 receptor antagonist SCH23390 (0.2, 0.6, and 2 mg/kg), the PDE‐IV activities in the striatum and frontal cortex were dose‐dependently suppressed in both age groups. However, the degree of suppression by SCH23390 was more marked in young than in aged monkeys. These results demonstrate that the striatal cAMP second‐messenger system activity as well as its functional response to dopamine D 1 antagonist showed age‐related impairment in the brain. Synapse 44:139–145, 2002. © 2002 Wiley‐Liss, Inc.