Unilateral up-regulation of glutamate receptors in limbic regions of amygdaloid-kindled rats

Abstract

Quantitative autoradiography was used to examine central binding sites for L-[3H]glutamate in amygdaloid-kindled rats since receptors for excitatory amino acids have been implicated in epileptiform activity and seizure behaviors. In tissue from rats killed five days after two kindled seizures, the ipsilateral hippocampus, entorhinal, perirhinal and parietal cortices had significantly (35-100%) greater densities of binding sites for L-[3H]glutamate than the opposite, contralateral side or operated, unstimulated controls. These regions receive excitatory inputs from the amygdala via the entorhinal cortex. Dissociation constants were not altered and significant differences were not observed in the binding parameters for L-[3H]glutamate between control and kindled rats or ipsilateral and contralateral sides of the amygdala, corpus striatum, nucleus accumbens or substantia nigra. The proportion and affinity of N-methyl-D-aspartate (NMDA)-sensitive binding sites for L-[3H]glutamate was unchanged after kindling, as were the relative proportions of kainate- and AMPA-(DL-alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid) sensitive sites. However, the density of NMDA and non-NMDA receptor subtypes was increased in the ipsilateral hippocampus, entorhinal, perirhinal and parietal cortices of kindled rats. These findings of specific, unilateral glutamate receptor up-regulation may indicate adaptive responses to the enhanced excitation found in kindling, and are consistent with other neuronal changes reported in early kindling.