Effect of MK-801 on seizures induced by exposure to hyperbaric oxygen: Comparison with AP-7

The effect of the noncompetitive(1) N-methyl-D-aspartate (NMDA)-receptor antagonist MK-801 on seizures induced by hyperbaric oxygen in relation to changes in cerebral blood flow (CBF) was investigated. Rats were injected with MK-801 (0.005-8 mg/kg) 30 min before exposure to 100% O-2 at 5 atm (gauge pressure). MK-801 administration resulted in a biphasic response in seizure latency. Doses of 0.1-4 mg/kg significantly decreased time to EEG and motor seizures, while 8 mg/kg had no effect on seizure latency. MK-801 had no effect on seizure duration. In a dose range 0.1-8 mg/kg MK-801 increased CBF in awake animals, which might be responsible for the decreased seizure latency. The gradual increase in seizure latency with increasing MK-801 doses suggests involvement of an additional factor probably related to the drug's anticonvulsive effect. Unlike MK-801, a competitive NMDA receptor antagonist, AP-7, at a dose 250 mg/kg had no effect on latency to seizures or CBF.