Ontogenetic study of metaphit-induced audiogenic seizures in rats

Ontogenetic differences in susceptibility to metaphit (1-(1-(3-isothiocyanatophenyl)cyclohexyl)-piperidine)-induced audiogenic seizures were examined in young, developing (ages: 12, 18, and 25 days) and adult (90 days old) Wistar albino rats. Metaphit was injected in a dose of 10 mg/kg i.p. and animals were subjected to intense audio stimulation (100 ± 3 dB, 60 s) at hourly intervals after administration. Audiogenic seizures (AGS) were scored according to a four point descriptive rating scale (0-3). AGS were elicited in all age groups; they were induced for 12, 15, 15, and 30 h in 12-, 18-, 25-day-old, and adult rats, respectively. Younger animals reached a peak incidence and severity of seizures before adult rats. Twenty-five-day-old rats showed greatest incidence and severity of seizures, and shortest latency. Twelve-day-old animals had longest latencies. Besides audiogenic seizures, we observed convulsions induced by metaphit only in the form of running episodes, forelimb clonus, clonic convulsions, and rearing. Results suggest that young rats develop metaphit-induced sound seizures more rapidly, but that adults have longer period of seizure susceptibility. Different susceptibility to seizures is probably due to changes in excitatory and inhibitory pathways, while maturation of blood-brain barrier is less probable, since metaphit has a lipophilic nature.