1. The blocking effects of
valproate (2-propylpentanoic acid), a standard anti-epileptic drug, on
metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]-
piperidine)-induced audiogenic
seizures as a model of generalized, reflex
audiogenic epilepsy in adult Wistar male rats were studied. 2. Rats were stimulated using an electric bell (100 +/- 3 dB, 5-8 kHz, 60 s) 60 min after i.p.
metaphit (10 mg/kg) injection and afterwards at hourly intervals. For power spectra and electroencephalograph (EEG) recordings, three
gold-plated screws were implanted into the skull. Different doses of
valproate (50, 75 and 100 mg/kg) were injected i.p. into rats with fully developed
metaphit seizures after the eighth audiogenic testing. 3. In
metaphit-treated animals, the EEG appeared as polyspikes, spike-wave complexes and sleep-like patterns, whereas the power spectra were increased compared with the corresponding controls. 4.
Valproate reduced the incidence and intensity of convulsions and prolonged the duration of the latency period in a dose-dependent manner 4 h after administration. 5. The ED(50) of
valproate in the first hour after injection was 63.19 mg/kg (95% confidence interval 51.37-77.71 mg/kg). 6. None of the doses of
valproate applied eliminated the EEG signs of
metaphit-provoked epileptiform activity. 7. Taken together, these results suggest that all doses of
valproate examined acted to suppresse behavioural but not epileptic EEG spiking activity in
metaphit-induced
seizures.