3H-L-glutamate binding and 3H-D-aspartate release from hippocampal tissue during the development of pentylenetetrazole kindling in rats

Previous studies have proposed that there is an increase in the density of glutamate binding sites after pentylenetetrazol (PTZ) kindling, whereas the glutamate release is not altered. Little is known about the time course of these changes. Therefore, we studied H-3-L-glutamate binding to hippocampal membranes and K+-stimulated H-3-D-aspartate release from hippocampal slices of rats given PTZ 3, 7, and 13 times up to a fully kindling state. After three PTZ injections, amino acid release from hippocampal tissue slices was significantly enhanced in comparison to controls, whereas H-3-L-glutamate binding was not altered. After seven injections of PTZ, specific glutamate binding to hippocampal membranes tended to increase, and K+-stimulated H-3-D-aspartate release from rat hippocampal slices was normalized. The kindled state characterized by generalized clonic-tonic seizures was reached after 13 PTZ injections, and it was accompanied by an enhancement in the density of glutamate binding sites, whereas the chemically evoked amino acid release remained unchanged. It can be concluded that the amino acid release is increased in the early phase of PTZ kindling development, whereas after completion of kindling, the density of excitatory amino acid binding sites is enhanced. (C) 1999 Elsevier Science Inc.