Increased mRNA expression for the alpha(1) subunit of the GABA(A) receptorfollowing nitrous oxide exposure in mice

The mechanisms by which nitrous oxide (N2O) produces physical dependence an d withdrawal seizures are not well understood, but both N2O and ethanol exe rt some of their effects via the GABA, receptor and several lines of eviden ce indicate that withdrawal from N2O and ethanol may be produced through si milar mechanisms. Expression levels of mRNA transcripts encoding several GA BA, receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N2O exposure would produce changes in mRNA expression for the a, subunit. Male, Swiss-Webster mice, 10-12 weeks of age, were expo sed for 48 h to either room air or a 75%:25% N2O:O-2 environment. Brains we re sectioned and mRNA for the alpha (1) subunit was detected by in situ hyb ridization using an S-35-labelled cRNA probe. N2O exposure produced a signi ficant increase in expression levels of the a, subunit mRNA in the cingulat e cortex, the CA1/2 region of the hippocampus, the dentate gyrus, the subic ulum, the medial septum, and the ventral tegmental area. These results lend support to the hypothesis that N2O effects are produced, at least in part, through the GABA, receptor and that N2O produces these effects through act ions in the cingulate cortex, hippocampus, ventral tegmental area and media l septum. These results are also further evidence that ethanol and N2O prod uce dependence and withdrawal through common mechanisms. (C) 2001 Published by Elsevier Science B.V.