Metaphit-induced audiogenic seizure and its inhibition by MK-801: electroencephalographic and behavioral characterization.

Abstract

Adult male Wistar rats were subjected to intense sound stimulation from an electric bell (100 dB and 12 KHz for 60 s) after a single intraperitoneal (i.p. 50 mg/kg) injection of metaphit [1-(1-/3 isothiocyanatophenyl-cyclohexyl) piperidine]. EEG recordings demonstrated appearance of paroxysmal activity and spike-wave complexes from cortical electrodes, with frequency and amplitude increasing with time. Metaphit-induced audiogenic seizures in the rats were tested 24 h after metaphit administration. The seizures consisted of wild running followed by clonic and tonic convulsions, and the seizure pattern could be elicited at hourly intervals for the next 24 h in all tested animals. Forty-eight hours after metaphit administration, susceptibility to sound stimulation began to decrease gradually. The first component of seizure response to disappear was tonic extension, followed by disappearance of clonic convulsion; the last component to disappear was running behavior. Each behavioral seizure response had a characteristic EEG correlate. After approximately 50 h, no animal responded to sound stimulation. The noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, MK-801 [5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate] was evaluated as an anticonvulsant against metaphit-induced audiogenic seizures in two experiments. In the first experiment, MK-801 was administered in a single dose of 0.5 mg/kg i.p. 23.5 h after metaphit injection and 30 min before sound stimulation, which completely blocked both the EEG and the behavioral response to sound stimulation for 37 h.(ABSTRACT TRUNCATED AT 250 WORDS)