N-METHYL-D-ASPARTATE-INDUCED ENHANCEMENT OF ACTIVATOR PROTEIN-1 DNA-BINDING ACTIVITY IS BLOCKED BY ETHANOL IN CEREBELLAR GRANULE CELLS

The effects of ethanol on N-methyl-D-aspartate (NMDA) and non-NMDA rec eptor agonist-stimulated activator protein-1 (AP-1) DNA binding activi ty in primary cultures of rat cerebellar granule cells were investigat ed. The application of intoxicating concentrations of ethanol produced a concentration-dependent inhibition of NMDA-enhanced AP-1 binding wi th a significant reduction obtained at 50 mM ethanol. The inhibitory a ctions of ethanol on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propio nic acid (AMPA)-stimulated AP-1 binding were considerably weaker as co mpared to the effects seen following administration of NMDA. The AMPA- induced enhancement of AP-1 DNA binding activity was demonstrated both in the absence and presence of cyclothiazide, a drug, which is known to block the desensitization of AMPA receptors. Our data suggest that moderate concentrations of ethanol modulate glutamate-induced alterati ons of gene expression in brain neurons.