Without oxygen, all mammals suffer neuronal injury and excitotoxic cell death mediated by over-activation of the glutamatergic N-methyl-D-aspartate receptor (NMDAR). The western painted turtle can survive anoxia for months and down-regulation of NMDAR activity is thought to be neuroprotective during anoxia. NMDAR activity is related to the activity of another glutamate receptor, the -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR). AMPAR blockade is neuroprotective against anoxic insult in mammals but the role of AMPARs in the turtles anoxia tolerance has not been investigated. To determine if AMPAR activity changes during hypoxia or anoxia in the turtle cortex, whole-cell AMPAR currents, AMPAR-mediated excitatory postsynaptic potentials (EPSPs) and excitatory postsynaptic currents (EPSCs) were measured. The effect of AMPAR blockade on normoxic and anoxic NMDAR currents was also examined. During 60 minutes of normoxia, evoked peak AMPAR currents and the frequencies and amplitudes of EPSPs and EPSCs did not change. During anoxic perfusion: evoked AMPAR peak currents decreased 59.2 ± 5.5 and 60.2 ± 3.5% at 20 and 40 mins, respectively, EPSP_f and amplitude decreased 28.7 ± 6.4% and 13.2 ± 1.7% respectively, and EPSC_f and amplitude decreased 50.7 ± 5.1% and 51.3 ± 4.7%, respectively. In contrast, hypoxic (PO₂ = 5%) AMPAR peak currents were potentiated 56.6 ± 20.5. All changes were reversed by re-oxygenation. AMPAR currents and EPSPs were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In neurons pre-treated with CNQX, anoxic NMDAR currents were reversibly depressed by 49.8 ± 7.9%. These data suggest that AMPARs may undergo channel arrest in the anoxic turtle cortex.