Substituting choline for sodium resulted in an extracellularly recorded transient depolarization and increased efflux of glutamate and adenosine from rat hippocampal slices. The depolarization was blocked by a combination of NMDA and non-NMDA antagonists, MK-801 (10 μM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 50 μM). Adenosine release was blocked by MK-801 alone. These data suggest that glutamate released as a result of the sodium removal acts at NMDA and non-NMDA glutamate receptors to trigger the depolarization and acts at NMDA receptors to trigger adenosine release.