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Updated: Sep 7, 2026
The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System
Published on: April 25, 2012
A reduced extracellular serotonin level increases the 5-HT1A PET ligand 18F-MPPF binding in the rat hippocampus
Luc Zimmer1, Latifa Rbah, Fabrice Giacomelli
1Centre d'Exploration et de Recherche Médicales par Emission de Positons, Biomedical Cyclotron, Lyon, France. zimmer@cermep.fr
Unlabelled:
4,2'-(Methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine ((18)F-MPPF) is a radiotracer used in clinical PET studies for the visualization of serotonin-1A (5-HT(1A)) receptors. In a previous study, we demonstrated that a rapid enhancement of extracellular serotonin concentrations influences (18)F-MPPF-specific binding. Because endogenous serotonin is significantly decreased in some pathologies, the aim of this study was to determine whether (18)F-MPPF is sensitive to depletion of this neurotransmitter.
Methods:
Using the beta-microprobe, an original beta(+)-sensitive intracerebral probe, and microdialysis, the effect of decreased serotonin on the specific binding of (18)F-MPPF to 5-HT(1A) receptors was investigated in the hippocampus of the anesthetized rat. Extracellular serotonin was pharmacologically decreased in the hippocampus after a single injection of p-ethynylphenylalanine ([p-EPA] 5 mg/kg), a new tryptophan hydroxylase inhibitor.
Results:
Our results showed that the (18)F-MPPF-specific binding was significantly enhanced after the decrease of extracellular serotonin. These results were confirmed by the (18)F-MPPF distribution in cerebral tissues (hippocampus-to-cerebellum ratio) and by the decrease of the extracellular (18)F-MPPF collected in hippocampal dialysates.
Conclusion:
This study further supports the view that (18)F-MPPF binding potential is increased in the hippocampus if the endogenous serotonin is pharmacologically decreased after a p-EPA injection. This phenomenon will be an additional factor in the interpretation of the results from (18)F-MPPF clinical PET studies.
