Comparative study of hippocampal neuronal loss and in vivo binding of 5-HT1a receptors in the KA model of limbic epilepsy in the rat

Abstract

A high density of 5-HT1a receptors is present in pyramidal hippocampal cells. Mapping of these receptors may be performed in vivo using the tracer no-carrier-added 4-(18)F-fluoro-N-2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl-N-2-pyridinyl-benzamide (MPPF). We tested the hypothesis of a relationship between MPPF binding and post-epileptic neuronal loss in the hippocampus. The model of limbic epilepsy induced by kainic acid (KA) in the rat was used. Rats were sacrificed at various times (1 h-240 days) after systemic injection of 10 mg/kg KA. Determination of MPPF binding in the brain was combined with a quantification of neuronal loss using DNA labeling with propidium iodide and confocal microscopy. Hippocampal MPPF binding varied according to time elapsed from KA injection. An initial decrease from day 1 to day 6 post injection was followed by a relative increase between day 6 and day 30. This effect was observed in rats which showed hippocampal neuronal loss but also in one rat which did not. In KA treated rats, statistically significant relationship between MPPF binding and neuronal count was found during the acute period (rats sacrificed 1 h-day 6 after KA injection) and the chronic phase (rats sacrificed beyond day 60 after KA injection). The late relative increase of MPPF binding suggests an epilepsy-induced increase of 5-HT1a receptors in the hippocampus. This effect needs to be further characterized before considering PET determination of hippocampal MPPF binding as a method of post-epileptic neuronal loss assessment.