Yamamoto Shigeyuki, Onoe Hirotaka, Tsukada Hideo, Watanabe Yasuyoshi
Department of Physiology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
Synapse. 2007 Sep;61(9):724-31. doi: 10.1002/syn.20422.
Using a combination of positron emission tomography (PET) and the microdialysis technique, the effects of increased endogenous serotonin (5-hydroxytryptamine; 5-HT) on the binding of [(11)C]DASB to 5-HT transporters (5-HTT) were investigated in the conscious monkey brain. Five rhesus monkeys (Macaca mulatta) were scanned with [(11)C]DASB under the control condition and the increased endogenous 5-HT condition, in which 5-hydroxy-L-tryptophan (5-HTP) was administered (20 mg/kg, i.v.) before the PET scan. Compared with the control scan, the 5-HTP administration significantly decreased the binding potential (BP) (BP = B(max)/K(d)) of [(11)C]DASB in several brain regions. The mean % decrease of BP was biggest in the caudate and putamen. Two monkeys were scanned with [(11)C]5-HTP to assess the amino acid decarboxylase (AADC) activity in the brain, resulting in the high activity in the caudate and putamen. Microdialysis measurements showed that although 5-HTP administration (20 mg/kg, i.v.) increased the extracellular 5-HT levels in both the prefrontal cortex and caudate, the increase of the 5-HT level in the caudate was 27 times higher than that in the prefrontal cortex. These results suggest that the caudate and putamen, both of which show high AADC activity, convert 5-HTP to 5-HT at a high rate, and the increased 5-HT competes with [(11)C]DASB for the 5-HTT.
采用正电子发射断层扫描（PET）与微透析技术相结合的方法，在清醒的猴脑中研究内源性血清素（5-羟色胺；5-HT）增加对[(11)C]DASB与5-羟色胺转运体（5-HTT）结合的影响。对5只恒河猴（猕猴）在对照条件下以及内源性5-HT增加的条件下进行[(11)C]DASB扫描，在内源性5-HT增加的条件下，于PET扫描前静脉注射5-羟-L-色氨酸（5-HTP，20mg/kg）。与对照扫描相比，注射5-HTP后，[(11)C]DASB在几个脑区的结合势（BP，BP = B(max)/K(d)）显著降低。尾状核和壳核的BP平均降低百分比最大。对2只猴子进行[(11)C]5-HTP扫描以评估脑内氨基酸脱羧酶（AADC）活性，结果显示尾状核和壳核活性较高。微透析测量结果表明，尽管静脉注射5-HTP（20mg/kg）可使前额叶皮质和尾状核的细胞外5-HT水平均升高，但尾状核中5-HT水平的升高幅度比前额叶皮质高27倍。这些结果表明，尾状核和壳核均具有较高的AADC活性，能将5-HTP快速转化为5-HT，增加的5-HT与[(11)C]DASB竞争5-HTT。
