Age-related effects of NMDA-stimulated concomitant release of nitric oxide and glutamate in cortical slices prepared from DBA/2 mice

Abstract

In this study we have used cortical slices prepared from genetically epilepsy-prone DBA/2 mice to investigate the effects of N-methyl- d-aspartate (NMDA) receptor stimulation on the concomitant release of nitric oxide (NO) and endogenous amino acids. DBA/2 mice exhibit an age-related susceptibility to audiogenic seizures so consequently we have compared the responses in 14–16-, 21–30- and 56–63-day-old mice. NMDA (200 μM) stimulated the release of NO and glutamate in slices prepared from 21–30-day-old animals. The release of both NO and glutamate was inhibited by the NO synthase inhibitor, l-N G-monomethylarginine ( l-N G-MMA), and by haemoglobin. There was no significant NMDA-stimulated release of NO or glutamate in slices prepared from 14–16- or 56–63-day-old mice. These results support a neuromodulator role for NO in the release of transmitter and also provide evidence that the age-related susceptibility of DBA/2 mice to audiogenic seizures is related to changes in sensitivity to NMDA receptor-mediated events.