Polyamine-enhanced NMDA receptor activity: effect of ethanol.

The effect of ethanol on spermidine-enhanced, N-methyl-D-aspartate (NMDA)-induced seizures and c-fos expression was investigated in the rat brain. The latency of tonic-clonic convulsions induced by i.p. administration of NMDA (50 mg/kg) was decreased by prior i.c.v. injection of spermidine (0.1-2.5 mumol) in a dose-dependent manner. Neither NMDA (50 mg/kg) nor spermidine (up to 2.5 mumol) alone induced c-fos mRNA expression in the brain. When both agents were administered, significant induction of c-fos expression occurred 30 min after the convulsion. Prior treatment with ethanol did not alter the curve of spermidine dose-dependency over most of the range. The c-fos expression induced by a combination of NMDA (50 mg/kg) and spermidine (1.0 mumol) was unaffected by ethanol. Only at a high dose of ethanol (2.0 g/kg) and at minimal spermidine enhancement was NMDA-induced seizure and c-fos expression inhibited. These results suggest that polyamines may have an important role in modulating NMDA receptor function in vivo and that polyamine enhancement of NMDA receptor function is relatively insensitive to the inhibitory effects of ethanol.