In vivo binding properties of [carbonyl-11C]WAY-100635: effect of endogenous serotonin.
[Carbonyl-(11)C]WAY-100635 has been reported to be a useful ligand for the investigation of 5-HT(1A) receptor imaging in vivo. However, the cellular distribution and the influence of endogenous serotonin (5-HT) on in vivo binding have not been fully examined. In this study, we investigated the effect of 5,7-dihydroxytryptamine-produced destruction of 5-HT neurons, reserpine-induced 5-HT depletion, and fenfluramine-induced 5-HT increase on [carbonyl-(11)C]WAY-100635 binding in vivo. There was no significant change in the uptake of [carbonyl-(11)C]WAY-100635 in the slice of 5-HT denervated rat brain except in the raphe nucleus, where 5-HT cell bodies exist. There was no obvious effect of enhanced 5-HT release by fenfluramine or decreased release by reserpine on [carbonyl-(11)C]WAY-100635 binding in the dissected brain region. No significant effect was observed in the time course of [carbonyl-(11)C]WAY-100635 in the hippocampus and frontal cortex measured by PET. These results indicated that the in vivo binding of [carbonyl-(11)C]WAY-100635 in the hippocampus and cerebral cortex mainly reflects postsynaptic 5-HT(1A) receptor binding, and that this binding is not sensitive to endogenous 5-HT.
CREST, Japan Science and Technology Corporation (JST), Chiba, Japan.
J
J
Maeda
T
T
Suhara
M
M
Ogawa
T
T
Okauchi
K
K
Kawabe
M R
MR
Zhang
J
J
Semba
K
K
Suzuki
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D010879:Piperazines / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D009498:Neurotoxins; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide