Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand binding sites in mouse cerebellar neurons following in vivo ethanol administration: an autoradiographic analysis.
The gamma-aminobutyric acidA (GABAA)/benzodiazepine (BZ) receptor is a pentamer composed of subunits belonging to several classes (alpha 1-6, beta 1-4, gamma 1-4, delta, and rho 1 and rho 2). In situ hybridization, radioligand autoradiography, and immunocytochemistry were used to examine GABAA/BZ receptor alpha 1, alpha 6, beta 2, beta 3, and gamma 2 subunit expression in murine Purkinje, granule, and deep cerebellar neurons after in vivo ethanol exposure. Chronic ethanol treatment resulted in decreased alpha 1 subunit mRNA expression in each cell type, whereas the expression of alpha 6 and gamma 2 subunit mRNA levels increased; no changes were observed in the expression of beta 2 and beta 3 subunit mRNA. GABA and BZ agonist binding and antibody staining paralleled the changes in mRNA levels. Acute ethanol injection resulted in increased expression of alpha 1 and beta 3 mRNAs, whereas levels of alpha 6, beta 2, and gamma 2 mRNAs remained stable. Our results indicate that, in cerebellar neurons, the expression of specific GABAA/BZ receptor subunit mRNAs, polypeptides, and binding sites is independently regulated by in vivo administration of alcohol. The observed changes were not restricted to any one cerebellar cell type, because subunit expression in Purkinje, granule, and deep cerebellar cells was similarly affected.
Wu
C H
CH
Department of Pharmacology, Ohio State University, Columbus 43210, USA.
Frostholm
A
A
De Blas
A L
AL
Rotter
A
A
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001665:Binding Sites; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009118:Muscimol / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D014316:Tritium
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014316:Tritium; D009118:Muscimol; D000431:Ethanol; D005445:Flunitrazepam