PMID: 11902118Mar 21, 2002Paper

Effect of endogenous serotonin on the binding of the 5-hT1A PET ligand 18F-MPPF in the rat hippocampus: kinetic beta measurements combined with microdialysis

Journal of Neurochemistry
Luc ZimmerJ F Pujol

Abstract

By using a combination of an original beta+-sensitive intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of 18F-MPPF [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido]ethyl]piperazine] to the serotonin-1A (5-HT1A) receptors was investigated in the hippocampus of the anaesthetized rat. Our beta-sensitive probe prototype was sensitive enough to obtain specific 18F-MPPF time-activity curves in the rodent (hippocampus/cerebellum ratio approximately 2). The serotonin neuronal release was pharmacologically enhanced using fenfluramine at three different doses (1, 2 and 10 mg/kg intravenous) multiplying by 2-15 the extracellular serotonin in the hippocampus. These extracellular variations of extracellular serotonin resulted in dose-ranging decreases in 18F-MPPF-specific binding in the same rat. Our results showed for the first time that 18F-MPPF binding could be modulated by modifications of extracellular serotonin in the rat hippocampus. These results were confirmed by the enhancement of extracellular radioactivity collected in dialysates after the displacement of 18F-MPPF by fenfluramine. After modelization, 18F-MPPF binding could constitute an interesting radiotracer...Continue Reading

Citations

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