Displacement of the PET ligand ¹⁸F‐MPPF by the electrically evoked serotonin release in the rat hippocampus

Abstract

The effects of the electrically evoked serotonin release were evaluated on the binding of (18)F-MPPF in the hippocampus of anesthetized rats. The specific binding of (18)F-MPPF was measured by an implanted beta-microprobe and the serotonin (5-HT) extracellular concentration was measured by microdialysis under the same conditions. Our results showed that the 10-, 20-, or 30-min electrical stimulation of the raphe nucleus elicited a significant increase in extracellular 5-HT, only detectable in the presence of a 5-HT reuptake inhibitor in the perfusate (5 microM clomipramine). Interestingly, the raphe stimulations were associated with a 27-76% reversible decrease of the (18)F-MPPF specific binding in the hippocampus, but an unchanged extracellular (18)F-MPPF collected in dialysates. Considered together, these observations suggest that (18)F-MPPF binding is sensitive to 5-HT released at a neuronal level. This compartment, explored by the beta-microprobe, is probably distinct from the extracellular compartment, explored by microdialysis.

The Potential of a Radiosensitive Intracerebral Probe to Monitor 18F-MPPF Binding in Mouse Hippocampus In Vivo

“…The time-radioactivity curves obtained with the b microprobe after intravenous 18 F-MPPF administration were reproducible between mice (coefficient of variation, approximately 15%), showing a clear distinction between the hippocampus and the cerebellum. The hippocampus-to-cerebellum ratio increased linearly with time, approaching a value of 3 at 15 min, consistent with previous PET studies on rats (10,11). This ratio is compatible for future radiopharmacologic studies on mice, such as studies of radiotracer displacement, competition studies, or comparisons of the BP values between groups.…”

“…Second, we characterized 29-methoxyphenyl-(N-29-pyridinyl)-p- 18 Ffluorobenzamidoethylpiperazine ( 18 F-MPPF) binding in the mouse brain with ex vivo autoradiography and performed an in vivo pharmacokinetics study in anesthetized mice. 18 F-MPPF is a well-known 5-hydroxytryptamine receptor 1A (5-HT 1A ) PET radiotracer used in preclinical studies on rats (10,11,12,16,17). 18 F-MPPF is particularly suited to the development of the b microprobe for mouse applications because we have already reported time-activity curves for this radioligand in the rat brain using b microprobe technology (10)(11)(12).…”

“…This lowcost technology, which was initially developed for PET measurements of the rat brain, has successfully been used in pharmacokinetic and pharmacodynamic studies (8)(9)(10)(11)(12) and for quantitative measurements of glucose metabolism or cerebral blood flow (13)(14)(15) in rats. Here, we report the development of this technology for use in mice.…”

“…18 F-MPPF is a well-known 5-hydroxytryptamine receptor 1A (5-HT 1A ) PET radiotracer used in preclinical studies on rats (10,11,12,16,17). 18 F-MPPF is particularly suited to the development of the b microprobe for mouse applications because we have already reported time-activity curves for this radioligand in the rat brain using b microprobe technology (10)(11)(12). In addition, this radiotracer is considered to be of great interest for mouse models presenting 5-HT 1A deregulations such as depression (18,19).…”

Highly sensitive assay for the measurement of serotonin in microdialysates using capillary high-performance liquid chromatography with electrochemical detection

“…We started using one mobile phase previously reported and containing OSA, an ion-pairing agent, as commonly employed for the measurement of both 5-HT and 5-HIAA in microdialysates [15]. At their initial conditions (0.15 mol/L NaH 2 PO 4 , 0.5 mmol/L EDTA, 0.025 mmol/L OSA, 12.5% methanol, pH adjusted to 3.8), we added KCl for an optimal use of the ISAAC reference electrode and we choose 35 • C as running temperature as recommended by the detector supplier.…”