Effect of endogenous serotonin on the binding of the 5-HT[sub 1A] PET ligand[sup 18] F-MPPF in the rat hippocampus: kinetic β measurements combined with microdialysis.

By using a combination of an original β[sup +] -sensitive␣intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of [sup 18] F-MPPF [4-(2′-methoxyphenyl)-1-[2′-[N -(2′′-pyridinyl)-p -fluorobenzamido]ethyl]piperazine] to the serotonin-1A (5-HT[sub 1A] ) receptors was investigated in the hippocampus of the anaesthetized rat. Our β-sensitive probe prototype was sensitive enough to obtain specific [sup 18] F-MPPF time–activity curves in the rodent (hippocampus/cerebellum ratio approx. 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 [sup 18] F-MPPF-specific binding in the same rat. Our results showed for the first time that [sup 18] F-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 [sup 18] F-MPPF by fenfluramine. After modelization, [sup 18] F-MPPF binding could constitute an interesting radiotracer for positron emission tomography in evaluating the serotonin endogenous levels in limbic areas of the human brain. [ABSTRACT FROM AUTHOR]