Increased mRNA Expression for the α1 Subunit of the GABAA Receptor Following Nitrous Oxide Exposure in Mice
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Molecular Brain Research
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The mechanisms by which nitrous oxide (N2O) produces physical dependence and withdrawal seizures are not well understood, but both N2O and ethanol exert some of their effects via the GABAA receptor and several lines of evidence indicate that withdrawal from N2O and ethanol may be produced through similar mechanisms. Expression levels of mRNA transcripts encoding several GABAA receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N2O exposure would produce changes in mRNA expression for the α1 subunit. Male, Swiss–Webster mice, 10–12 weeks of age, were exposed for 48 h to either room air or a 75%:25% N2O:O2 environment. Brains were sectioned and mRNA for the a subunit was detected by in situ hybridization using an 35S-labelled cRNA probe. N2O exposure produced a significant increase in expression levels of the α1 subunit mRNA in the cingulate cortex, the CA1/2 region of the hippocampus, the dentate gyrus, the subiculum, 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 GABAA receptor and that N2O produces these effects through actions in the cingulate cortex, hippocampus, ventral tegmental area and medial septum. These results are also further evidence that ethanol and N2O produce dependence and withdrawal through common mechanisms.