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

A high density of 5-HT1a receptors is present in pyramidal hippocampal cell s. Mapping of these receptors may be performed in vivo using the tracer no- carrier-added 4-F-18-fluoro-N-2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl-N- 2-pyridinyl-benzamide (MPPF). We tested the hypothesis of a relationship be tween 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 injecti on 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 io dide and confocal microscopy. Hippocampal MPPF binding varied according to time elapsed from KA injection. An initial decrease from day 1 to day 6 pos t injection was followed by a relative increase between day 6 and day 30. T his effect was observed in rats which showed hippocampal neuronal loss but also in one rat which did not. In KA treated rats, statistically significan t relationship between MPPF binding and neuronal count was found during the acute period (rats sacrificed 1 h-day 6 after KA injection) and the chroni c phase (rats sacrificed beyond day 60 after KA injection). The late relati ve increase of MPPF binding suggests an epilepsy-induced increase of 5-HT1a receptors in the hippocampus. This effect needs to be further characterize d before considering PET determination of hippocampal MPPF binding as a met hod of post-epileptic neuronal loss assessment. (C) 2001 Elsevier Science B .V. All rights reserved.