Increased mRNA expression for the alpha(1) subunit of the GABA(A) receptor following nitrous oxide exposure in mice.
The mechanisms by which nitrous oxide (N(2)O) produces physical dependence and withdrawal seizures are not well understood, but both N(2)O and ethanol exert some of their effects via the GABA(A) receptor and several lines of evidence indicate that withdrawal from N(2)O and ethanol may be produced through similar mechanisms. Expression levels of mRNA transcripts encoding several GABA(A) receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N(2)O exposure would produce changes in mRNA expression for the alpha(1) subunit. Male, Swiss--Webster mice, 10--12 weeks of age, were exposed for 48 h to either room air or a 75%:25% N(2)O:O(2) environment. Brains were sectioned and mRNA for the alpha(1) subunit was detected by in situ hybridization using an 35S-labelled cRNA probe. N(2)O exposure produced a significant increase in expression levels of the alpha(1) 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 N(2)O effects are produced, at least in part, through the GABA(A) receptor and that N(2)O 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 N(2)O produce dependence and withdrawal through common mechanisms.
Johanek
L M
LM
Department of Biomedical Sciences, Marquette University, PO Box 1881, Milwaukee, WI 53201-1881, USA.
Cullinan
W E
WE
Vaughn
L K
LK
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009609:Nitrous Oxide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics*; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D009609:Nitrous Oxide