Glutamate-induced neurotoxicity is increased in cerebellar granule cells exposed chronically to ethanol

Chronic exposure of primary cultures of cerebellar granule cells to ethanol has previously been shown to result in an enhanced response of the cells to N-methyl-D-aspartate (NMDA). To determine if this increase in NMDA receptor function alters glutamate-induced cytotoxicity, cells were incubated in the presence or absence of 100 mM ethanol for 3 days, the ethanol was removed, the cells were treated with glutamate, and cell survival was assessed with fluorescein diacetate fluorescence. The ethanol-treated cells showed a significantly increased cytotoxic response to glutamate. Treatment with receptor-selective antagonists demonstrated that the cytotoxicity was mediated by NMDA receptors. The increased vulnerability to glutamate-induced cytotoxicity in ethanol-exposed cells may underlie the neuronal degeneration observed in animals and humans after chronic ethanol intake and withdrawal.