Long-term alterations in NMDA-sensitive L-[3H]glutamate binding in the rat hippocampus following fimbria-fornix lesioning.

Subcortical deafferentation of the rat hippocampus has been suggested to offer a model for developing limbic epilepsy. In the present study, the long-term effect of fimbria-fornix lesioning on the density and distribution of hippocampal N-methyl-D-aspartate (NMDA)-sensitive L-[3H]glutamate binding was studied using quantitative autoradiography. Compared to controls of the same age, the fimbria-fornix-lesioned (FFL) rats showed 1 year after lesioning a uniform, 20-33% increase in NMDA receptor density throughout the hippocampus, which was statistically significant in the stratum radiatum of the CA1 area (P = 0.001 and P < 0.05) and in the inner and outer halves of the dentate molecular layer (P < 0.05 for both). The increased receptor density in the FFL rats may reflect a long-term process of regeneration within the hippocampal formation, which could partly account for the maintenance or development of epileptogenity. The control animals, which were over 1 year old, showed lower binding density than young animals in all areas measured, thus suggesting a decrease in NMDA receptor binding during normal aging.