Ethanol inhibits NMDA-receptor mediated regulation of immediate early gene expression

The expression of c-fos mRNA in rat brain was induced by intraperitoneal (ip) administration of N-methyl-D-aspartate (NMDA) and kainic acid, agonists of different classes of glutamate receptors and by caffeine, an antagonist of adenosine receptors. The actions of NMDA but not kainic acid or caffeine were blocked by ethanol. Chronic exposure to ethanol vapour did not increase c-fos expression. However, ethanol-withdrawn rats showed a marked increase in c-fos expression. In situ hybridisation and immunohistochemistry indicated the expression was widely distributed in the brain but particularly in the cortex, hippocampus and the cerebellum. There was no marked change in the sensitivity of the NMDA receptor to inhibition by ethanol after chronic ethanol treatment. The withdrawal-induced expression of c-fos mRNA could be inhibited by prior administration of MK801. These results emphasise the NMDA receptor as an important site of ethanol action and the potential use of immediate early gene expression in neuropharmacology in vivo.