Metaphit-induced audiogenic seizure and its inhibition by MK-801: electroencephalographic and behavioral characterization.
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)
Susić
V T
VT
Institute of Medical Physiology, Belgrade University, Faculty of Medicine, Yugoslavia.
Marković
O
O
Lipovac
M N
MN
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004576:Electromyography / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017478:Receptors, Phencyclidine / Q000187:drug effects; D012640:Seizures / Q000209:etiology* / Q000517:prevention & control
D017478:Receptors, Phencyclidine; D016291:Dizocilpine Maleate; C044705:metaphit; D010622:Phencyclidine