THE EFFECT OF FLUMAZENIL ON CNS OXYGEN-TOXICITY IN THE RAT

The toxicity of hyperbaric oxygen in the central nervous system is exp ressed by generalized tonic-clonic seizures. In the search for drugs e ffective against these seizures, we tested flumazenil, a benzodiazepin e antagonist known to have antiepileptic properties. Ferry rats with c hronic cortical electrodes were injected i.p. with one of three doses of flumazenil (0.2, 2, and 20 mg/kg) or their vehicle, before exposure to 0.5 MPa oxygen. EEG and the spectral analysis of background EEG ac tivity were monitored. The duration of the latent period until the app earance of electrical discharges in the EEG was used as an index oxyge n toxicity. Significantly prolongation of the latent period preceding oxygen seizures was noted in the group of rats treated with 0.2 mg/kg flumazenil (p < 0.05 in Tukey test). However, when the dose of flumaze nil was increased, the duration of the latent period returned to contr ol values. These diverse effects of flumazenil on the benzodiazepine r eceptor may account for its complex effects on hyperoxic-induced seizu res.