General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex

The effects of several general anaesthetics on the responses evoked by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) were investigated in mouse cortical wedges placed in a two compartment bath and superfused with a nominally Mg(2+)-free Krebs solution. Chloroform (3-6 mM) and halothane (1-3 mM) preferentially antagonized AMPA responses; thiopental (0.1-0.4 mM), diethyl ether (10-30 mM) and isoflurane (1-3 mM) antagonized both AMPA or NMDA responses while ketamine antagonized NMDA responses in a highly selective way. The antagonism of the excitatory amino acid responses exerted by the anaesthetics was non competitive in nature. The inhibition of excitatory amino acid receptor function may be one of the mechanisms whereby general anaesthesia is produced.