The potential of the β-Microprobe, an intracerebral radiosensitive probe, to monitor the [18F]MPPF binding in the rat dorsal raphe nucleus
Résumé
The aim of this study was to demonstrate the ability of a recently developed #+-range sensitive intracerebral probe (#-Microprobe) to measure the binding kinetics of [18F]MPPF, a well-documented 5-HT1A serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT1A receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the #-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal #-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [18F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [18F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [18F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT1A antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using #-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [18F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [18F]MPPF in the DRN of anaesthetised rodents.