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Effect of endogenous serotonin on the binding of the 5‐HT 1A PET ligand 18 F‐MPPF in the rat hippocampus: kinetic β measurements combined with microdialysis
Author(s) -
Zimmer Luc,
Mauger Gweltas,
Le Bars Didier,
Bonmarchand Gregory,
Luxen André,
Pujol JeanFrançois
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.0022-3042.2001.00696.x
Subject(s) - microdialysis , serotonin , extracellular , fenfluramine , chemistry , hippocampus , 5 ht receptor , medicine , extracellular fluid , neurotransmitter , pharmacology , endocrinology , biophysics , receptor , biochemistry , biology
By using a combination of an original β + ‐sensitive␣intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of 18 F‐MPPF [4‐(2′‐methoxyphenyl)‐1‐[2′‐[ N ‐(2′′‐pyridinyl)‐ p ‐fluorobenzamido]ethyl]piperazine] to the serotonin‐1A (5‐HT 1A ) receptors was investigated in the hippocampus of the anaesthetized rat. Our β‐sensitive probe prototype was sensitive enough to obtain specific 18 F‐MPPF time–activity curves in the rodent (hippocampus/cerebellum ratio ≈ 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 18 F‐MPPF‐specific binding in the same rat. Our results showed for the first time that 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 18 F‐MPPF by fenfluramine. After modelization, 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.