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  • Title: Effects of increased endogenous serotonin on the in vivo binding of [11C]DASB to serotonin transporters in conscious monkey brain.
    Author: Yamamoto S, Onoe H, Tsukada H, Watanabe Y.
    Journal: Synapse; 2007 Sep; 61(9):724-31. PubMed ID: 17559093.
    Abstract:
    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.
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