Effect of endogenous serotonin on the binding of the 5-HT1A PET ligand 18F-MPPF in the rat hippocampus: kinetic β measurements combined with microdialysis
Article first published online: 27 FEB 2002
Journal of Neurochemistry
Volume 80, Issue 2, pages 278–286, January 2002
How to Cite
Zimmer, L., Mauger, G., Le Bars, D., Bonmarchand, G., Luxen, A. and Pujol, J.-F. (2002), Effect of endogenous serotonin on the binding of the 5-HT1A PET ligand 18F-MPPF in the rat hippocampus: kinetic β measurements combined with microdialysis. Journal of Neurochemistry, 80: 278–286. doi: 10.1046/j.0022-3042.2001.00696.x
- Issue published online: 27 FEB 2002
- Article first published online: 27 FEB 2002
- Received August 13, 2001; revised manuscript received October 10, 2001; accepted October 13, 2001.
- β microprobe;
- 5-HT1A receptors;
By using a combination of an original β+-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 β-sensitive probe prototype was sensitive enough to obtain specific 18F-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 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.