N-Methyl-D-aspartic acid- and metaphit-induced audiogenic seizures in rat model of seizures.
The effects of NMDA (N-methyl-D-aspartic acid) on metaphit (1-[1(3-isothiocyanatophenyl)-cyclohexyl]piperidine)-induced audiogenic seizures in adult male Wistar albino rats were studied with the aim of developing a suitable animal model of seizures. The animals were divided into four experimental groups: 1, saline control; 2, metaphit-injected; 3, metaphit + NMDA administered and 4, NMDA-treated. Upon the treatment, the rats were exposed to sound stimulation (100 +/- 3 dB, for 60 s) at hourly intervals and the incidence and severity (running, clonus and tonus) of seizures were analysed. In group 3, only the animals which did not exhibit any metaphit-induced audiogenic seizures over 8 h were given a subconvulsive NMDA dose after the eighth audiogenic testing. For EEG recordings, three gold-plated screws were implanted into the rat skull. In most animals, metaphit led to EEG abnormalities and elicited epileptiform activity recorded as spikes, polyspikes and spike-wave complexes. Maximum incidence and severity of metaphit-induced convulsions occurred 8 h after injection (incidence 9/12), abating gradually until disappearing 30 h later. NMDA alone provoked no seizure response but the initial signs characterized by isolated spike activity evolving into sporadic slow-wave complexes, thus representing a proconvulsive brain state, were observed. This compound led to stereotyped behaviour seen as asymmetric posture, loss of righting reflex and tonic hind limb extension lasting for 60-90 min. It also potentiated metaphit-induced audiogenic seizures. Potentiation of metaphit-related audiogenic seizures by NMDA was recorded in three out of 17 rats that had never displayed seizures in eight previous testings, with a maximum incidence of eight out of 17 animals, 13-14 h after metaphit administration and seizures lasted for 10 h.
Stanojlović
O
O
Department of Physiology, School of Medicine, University of Belgrade, 11000 Belgrade, Yugoslavia. vstanoj@eunet.yu
Zivanović
D
D
Susić
V
V
D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*
D016202:N-Methylaspartate; C044705:metaphit; D010622:Phencyclidine