Effects of increased endogenous serotonin on the in vivo binding of [11C]DASB to serotonin transporters in conscious monkey brain
Article first published online: 8 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 61, Issue 9, pages 724–731, September 2007
How to Cite
Yamamoto, S., Onoe, H., Tsukada, H. and Watanabe, Y. (2007), Effects of increased endogenous serotonin on the in vivo binding of [11C]DASB to serotonin transporters in conscious monkey brain. Synapse, 61: 724–731. doi: 10.1002/syn.20422
- Issue published online: 8 JUN 2007
- Article first published online: 8 JUN 2007
- Manuscript Received: 26 SEP 2007
- Manuscript Accepted: 17 FEB 2007
- CREST, JST (Saitama, Japan)
- serotonin transporter (SERT);
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.