PRESERVATION OF HIPPOCAMPAL NMDA RECEPTORS MAY BE CRUCIAL FOR SPATIAL-LEARNING AFTER EPILEPTIC SEIZURES IN RATS

Sustained electrical stimulation of the perforant pathway (PP) was use d to induce hippocampal seizures in conscious rats. About 4.5 h prior to stimulation, animals were given i.p. injections of either saline or CGP 39551 (10 mg/kg), a competitive antagonist of the N-methyl-D-aspa rtate (NMDA) receptor. When tested 2 weeks later in water maze, the sa line pretreated rats showed a severe impairment in spatial learning wh ereas the animals treated with CGP 39551 had the same escape latencies as the non-stimulated controls. Histological evaluation of cellular d egeneration revealed that the number of somatostatin-immunoreactive (S OM-IR) neurons in both stimulated groups was reduced almost equally, b ut in the CGP 39551 treated animals pyramidal cell damage was partly p rotected. However, in contrast to the placebo group, NMDA-sensitive [H -3]glutamate binding in strata radiatum and oriens of the CA1 area was not significantly reduced in the CGP 39551 group. Thus, the present r esults suggest that the CGP 39551 treatment was able to protect agains t the delayed phase of the excitotoxic cell damage, and that the prese rvation of NMDA receptors partly accounts for the good learning abilit y of the CGP 39551 pretreated, PP-stimulated rats.