In vivo binding properties of [carbonyl‐11C]WAY‐100635: Effect of endogenous serotonin

[Carbonyl‐11C]WAY‐100635 has been reported to be a useful ligand for the investigation of 5‐HT1A 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‐11C]WAY‐100635 binding in vivo. There was no significant change in the uptake of [carbonyl‐11C]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‐11C]WAY‐100635 binding in the dissected brain region. No significant effect was observed in the time course of [carbonyl‐11C]WAY‐100635 in the hippocampus and frontal cortex measured by PET. These results indicated that the in vivo binding of [carbonyl‐11C]WAY‐100635 in the hippocampus and cerebral cortex mainly reflects postsynaptic 5‐HT1A receptor binding, and that this binding is not sensitive to endogenous 5‐HT. Synapse 40:122–129, 2001. © 2001 Wiley‐Liss, Inc.

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