NMDA ANTAGONISTS INCREASE RECOVERY OF EVOKED-POTENTIALS FROM SLICES OF RAT OLFACTORY CORTEX AFTER ANOXIA

1 The role of glutamate in producing tissue damage during cerebral ano xia was investigated in brain slices using antagonists to the NMDA and AMPA receptor types. 2 Tissue function was assessed by field recordin gs of the synaptically evoked potentials elicited by stimulating the m ain afferent input to the olfactory cortex, the lateral olfactory trac t. Anoxia was produced by bathing the slice in glucose-free solution e quilibrated with 95% N2/5% CO2. 3 The amount of recovery of the evoked potential was inversely dependent on the period of anoxia and tempera ture: at 24-degrees-C, 15 min of anoxia followed by reoxygenation prod uced a 14.6 +/- 4.1% recovery whereas there was no recovery at 35-degr ees-C. 4 Dizocilpine and ketamine had no effect on synaptic transmissi on in oxygenated media but following anoxia they produced an increased recovery of the responses: from 14.6 +/- 4.1% to 48.3 +/- 7.8% for di zocilpine (10 muM) and 21.6 +/- 7.7% to 87.2 +/- 7.1% for ketamine (20 0 muM); the tissue endurance to anoxia was increased by around 5 min. 5 Blockade of the AMPA receptors did not influence recovery in spite o f the depressed synpatic transmission. A similar synaptic attenuation produced by lignocaine provided some increase in postanoxic recovery. 6 The NMDA receptor antagonist, AP5, antagonized NMDA at 50 muM by 3.7 fold and al 200 muM by 15 fold but only 200 muM increased post-anoxic recovery. This suggests that a substantial degree of NMDA antagonist is required before anoxic tissue damage due to NMDA receptor activatio n can be nullified. The antagonist to the glycine binding site, 7-chlo rokynurenic acid also increased recovery. 7 These in vitro experiments confirm the idea that NMDA receptor activation makes a substantial co ntribution to cerebral tissue damage and that this can be reduced by a substantial blockade of these receptors.