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 (N O) produces physical dependence and withdrawal seizures are not well understood, but 2 both N O and ethanol exert some of their effects via the GABA receptor and several lines of evidence indicate that withdrawal from 2 A N O and ethanol may be produced through similar mechanisms. Expression levels of mRNA transcripts encoding several GABA 2 A receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N O exposure would produce changes in 2 mRNA expression for the a subunit. Male, Swiss–Webster mice, 10–12 weeks of age, were exposed for 48 h to either room air or a 1 75%:25% N O:O environment. Brains were sectioned and mRNA for the a subunit was detected by in situ hybridization using an 2 2 1 35S-labelled cRNA probe. N O exposure produced a significant increase in expression levels of the a subunit mRNA in the cingulate 2 1 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 N O effects are produced, at least in part, through the GABA receptor and that N O produces 2 A 2 these effects through actions in the cingulate cortex, hippocampus, ventral tegmental area and medial septum. These results are also further evidence that ethanol and N O produce dependence and withdrawal through common mechanisms. Ó 2001 Published by 2 Elsevier Science B.V.