Effects of increased endogenous serotonin on the in vivo binding of [11C]DASB to serotonin transporters in conscious monkey brain

Authors

  • Shigeyuki Yamamoto,

    Corresponding author
    1. Department of Physiology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan
    2. Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
    • Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
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  • Hirotaka Onoe,

    1. RIKEN Frontier Research System Molecular Imaging Research Program, Kobe, Japan
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  • Hideo Tsukada,

    1. Central Research Laboratory, Hamamatsu Photonics KK, Hamamatsu, Shizuoka 434-8601, Japan
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  • Yasuyoshi Watanabe

    1. Department of Physiology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan
    2. RIKEN Frontier Research System Molecular Imaging Research Program, Kobe, Japan
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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 [11C]DASB to 5-HT transporters (5-HTT) were investigated in the conscious monkey brain. Five rhesus monkeys (Macaca mulatta) were scanned with [11C]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 = Bmax/Kd) of [11C]DASB in several brain regions. The mean % decrease of BP was biggest in the caudate and putamen. Two monkeys were scanned with [11C]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 [11C]DASB for the 5-HTT. Synapse 61:724–731, 2007. © 2007 Wiley-Liss, Inc.

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