SPECIFIC [H-3] GLUTAMATE BINDING IN THE CEREBRAL-CORTEX AND HIPPOCAMPUS OF RATS DURING DEVELOPMENT - EFFECT OF HOMOCYSTEINE-INDUCED SEIZURES

Specific [H-3]glutamate binding to synaptic membranes from the cerebra l cortex and hippocampus of 7-, 12- and 18-day-old rats was examined, both in control animals and during seizures induced by homocysteine. I n the cerebral cortex a transient peak of glutamate binding was observ ed in 7-day-old group, whereas in the hippocampus it occurred in 12-da y-old animals. Total specific [H-3]glutamate binding was not influence d by preceding seizure activity in either of the age groups and both t he studied regions. NMDA- and QA-sensitive glutamate bindings represen t the highest portion of the total binding. Moreover, NMDA-sensitive b inding in the cerebral cortex of 7-day-old rats is significantly highe r as compared to the two more mature groups. The proportion of individ ual receptor subtypes on total binding in each age group was not influ enced by preceding seizure activity. However, NMDA-sensitive binding i n the hippocampus of 12-day-old rats, sacrificed during homocysteine-i nduced seizures, was significantly increased as compared to correspond ing controls. In contrast to the effect of NMDA, AMPA, kainate and qui squalate which displaced to a different extent [H-3]glutamate binding, homocysteine had no effect when added to membrane preparations. Simil arly, [H-3]CPP and [H-3]AMPA bindings were not affected in the presenc e of homocysteine. It thus seems unlikely that homocysteine is an effe ctive agonist for conventional ionotropic glutamate receptors. Its pot ential activity at some of the modulatory sites at the NMDA receptor c hannel complex or at metabotropic receptors has to be clarified in fur ther experiments.