The effect of the competitive antagonist of the
N-methyl-D-aspartate (
NMDA) receptor, (+/-)
2-amino-7-phosphonoheptanoic acid (APH) on electrocorticographic (ECoG) activity and behavior was studied in the model of
epilepsy induced by systemic application of
metaphit (1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male Wistar rats were injected with
metaphit intraperitoneally (10 mg/kg, i.p.), and exposed to intense audio stimulation (electric bell generating 100 +/- 3 dB at animal level for 60 s) 1 h after administration and at 1-h intervals thereafter. ECoG tracings showed appearance of paroxysmal activity in form of spikes, spike-wave complexes and ECoG
seizures. Audiogenic
seizures consisted of wild running followed by clonic and tonic convulsions. Each behavioral seizure response had a characteristic ECoG correlate. The incidence 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 mumol icv in 5 microL of sterile saline) after the 8th hour of audiogenic testing (AGS). APH inhibited
seizures in a dose-dependent manner. The minimum dose which blocked
seizures in all animals was 0.03 mumol. However, ECoG signs of seizure susceptibility were not suppressed by APH. After varying periods of time, behavioral
seizures reappeared. It seems that APH blocks epileptiform propagation, but has less influence on the epileptogenic activity caused by
metaphit.