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.

Full 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 for positron emission tomography in evaluating the serotonin endogenous levels in limbic areas of the human brain.

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Author information

Author/s: Zimmer, Luc (L); Mauger, Gweltas (G); Le Bars, Didier (D); Bonmarchand, Gregory (G); Luxen, André (A); Pujol, Jean-François (JF);

Affiliation: CERMEP Biomedical Cyclotron, Lyon, France. zimmer(-atsign-)cermep.fr

Journal and publication information

Publication Type: Journal Article

Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)

Reference: 2002-Jan; vol 80 (issue 2) : pp 278-86

Dates: Created 2002/03/20; Completed 2002/04/04; Revised 2004/11/17;

PMID: 11902118, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Binding, Competitive
Cerebellum - metabolism
Extracellular Space - metabolism
Fenfluramine - pharmacology
Hippocampus - metabolism
Humans
Male
Microdialysis
Piperazines - pharmacokinetics; pharmacology

Piperazines - pharmacokinetics; pharmacology
Pyridines - pharmacokinetics; pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Serotonin - metabolism
Receptors, Serotonin, 5-HT1
Serotonin - metabolism
Serotonin Agents - pharmacology
Serotonin Antagonists - pharmacology
Tomography, Emission-Computed

Associated Chemicals: 4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine (0) ; Piperazines (0) ; Pyridines (0) ; Receptors, Serotonin (0) ; Receptors, Serotonin, 5-HT1 (0) ; Serotonin Agents (0) ; Serotonin Antagonists (0) ; WAY 100635 (146714-97-8) ; Fenfluramine (458-24-2) ; Serotonin (50-67-9)

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