QUANTITATIVE AUTORADIOGRAPHIC LOCALIZATION OF BINDING-SITES TO EXCITATORY AND INHIBITORY RECEPTORS IN EPILEPTIC-DAMAGED HIPPOCAMPUS

Abnormalities within different transmitter systems may contribute to t he brain damage seen in epilepsy and to the epileptogenesis. In order to elucidate the distribution of excitatory and inhibitory transmitter receptors, quantitative receptor autoradiography was performed in hum an hippocampi (n = 9) resected at surgery for temporal lobe epilepsy ( TLE) and in nonepileptic autopsy controls (n = 6). Tissue pathology wa s studied in parallel to evaluate the relationship between receptor de nsities and neuronal loss. The binding to the excitatory N-methyl-D-as partate (NMDA) receptor/channel site and to the muscarinic cholinergic receptor was measured. Inhibitory receptors chosen for study were the gamma-aminobutyric acid type A (GABA(A)) and benzodiazepine (BZ). The re was a strong correlation between reduced receptor binding and neuro nal loss. A general reduction in binding to all receptors was seen in epileptic patients compared to controls, most pronounced in the cornu ammonis (CA) 1, the area with most severe sclerosis. There was a great er relative reduction in binding to excitatory receptors than to inhib itory receptors. NMDA/channel receptor binding was reduced between 68% and 98% and muscarinic receptor binding between 32% and 75% in differ ent hippocampal regions. The corresponding reduction to GABA(A) recept ors was 3%-65% and to BZ receptors 0%-81%. These data may support the theory that brain damage seen in TLE is caused by excessive excitatory activation.