APH, AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, BLOCKS THE METAPHIT-INDUCED AUDIOGENIC-SEIZURES IN RATS

The effect of the competitive antagonist of the N-methyl-D-aspartate ( NMDA) receptor? (+/-)2-amino-7-phosphonoheptanoic acid (APH) on electr ocorticographic (ECoG) activity and behavior was studied in the model of epilepsy induced by systemic application of metaphit -(3-isothiocya natophenyl)-cyclohexyl)-piperidine). Male Wistar rats were injected wi th metaphit intraperitoneally (10 mg/kg, ip), and exposed to intense a udio stimulation (electric bell generating 100 +/- 3 dB at animal leve l for 60 s) 1 h after administration and at I-h intervals thereafter. ECoG tracings showed appearance of paroxysmal activity in form of spik es, spike-wave complexes and ECoG seizures. Audiogenic seizures consis ted of wild running followed by clonic and tonic convulsions. Each beh avioral seizure response had a characteristic ECoG correlate. The inci dence and severity of seizures increased with time, reaching a peak 8- 12 h after metaphit administration, and then gradually decreased until 31 h, when no animal responded to sound stimulation. APH was injected intracerebroventricularly (0.005, 0.01, 0.02, 0.03 and 0.05 mu mol ic v in 5 mu L of sterile saline) after the 8th hour of audiogenic testin g (AGS). APH inhibited seizures in a dose-dependent manner. The minimu m dose which blocked seizures in all animals was 0.03 mu mol. However, ECoG signs of seizure susceptibility were not suppressed by APH. Afte r varying periods of time, behavioral seizures reappeared. It seems th at APH blocks epileptiform propagation, but has less influence on the epileptogenic activity caused by metaphit.