The effect of flumazenil on CNS oxygen toxicity in the rat

The toxicity of hyperbaric oxygen in the central nervous system is expressed by generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested flumazenil, a benzodiazepine antagonist known to have antiepileptic properties. Forty rats with chronic 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 activity were monitored. The duration of the latent period until the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. Significant 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 flumazenil was increased, the duration of the latent period returned to control values. These diverse effects of flumazenil on the benzodiazepine receptor may account for its complex effects on hyperoxic-induced seizures.