Moderate hypoxia reduces pentylenetetrazol-induced seizures

Mice were exposed to an atmosphere consisting of 7% O2 and 93% N2 or 5.5% O2 and 94.5% N2 for 60 min. The susceptibility of the mice to the convulsive effect of pentylenetetrazol (PTZ) was decreased, in comparison to that of naive or sham-exposed controls, 1 and 7 days after exposure to 7% O2. A significant protective effect against PTZ-induced seizures was not observed in mice exposed to 5.5% O2. N-methyl-D-aspartate (NMDA) administrated immediately after exposure to the hypoxic atmosphere, had no significant influence on the protective effect of hypoxia. Treatment of naive or sham-exposed mice with NMDA resulted in protection against PTZ-induced seizures when they were tested 7 days later. Dizolcipine (MK 801), at a dose of 0.01 mg/kg injected i.p. 10 min before hypoxia, abolished the protective effect of hypoxia; higher doses (0.1 or 0.3 mg/kg) of MK 801 were not effective. The adenosine A1 receptor antagonist 1,3-diethyl-8-phenylxanthine (DPX), administered at a dose of 0.1 mg/kg s.c. before hypoxia, blocked the decrease in the susceptibility to the convulsive effect of PTZ. DPX also blocked the protective effect, seen after 7 days, of NMDA given to control mice. These results suggest that both NMDA and adenosine A1 receptor-mediated processes were involved in the protective effect of moderate hypoxia against PTZ-evoked seizure.