The senescence-accelerated mouse (SAM-P/8) is known as a murine model of aging and memory dysfunction. In the hippocampus and cerebral cortex of P/8, the contents of glutamic acid and glutamine were significantly higher than those of normal strain R/1 during 2 and 14 months. High K+-evoked endogenous glutamic acid release from the slices of P/8 was increased in comparison with R/1 at 9 and 11 months. In addition, the B(max) of [H-3]dizocilpine (MK-801, channel blocker for N-methyl-D-aspartic acid receptor/channel) binding in the cerebral cortex was age-dependently decreased in P/8 but not in R/1. These results suggest that synaptic dysfunctions in the glutamatergic system occur in the CNS of SAM-P/8.