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

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.