Effects of continuous diazepam administration on GABAA subunit mRNA in rat brain.

Published

Journal Article

Rats treated chronically with diazepam develop tolerance to diazepam effects and show changes in sensitivity of GABAergic systems. In order to investigate possible molecular mechanisms associated with these changes, we have evaluated the effects of acute and chronic diazepam treatment on levels of mRNA for the alpha 1 and beta 1 subunits of the GABAA receptor. Northern blots were hybridized with 32P-labeled GABA alpha 1 and beta 1 cDNA probes, and resulting bands were quantified by autoradiography and densitometry. Levels of alpha 1 mRNA were significantly decreased in cerebral cortex but not in cerebellum or hippocampus of chronic diazepam-treated rats. Acute diazepam treatment did not change levels of alpha 1 mRNA in any of the brain regions. Levels of beta 1 mRNA were examined by Northern blot analysis and also by solution hybridization analysis using a 32P-labeled riboprobe. Both methods showed that beta 1 mRNA was not significantly changed by chronic diazepam treatment. These results demonstrate a specific change in alpha 1 subunit that is associated with a state of altered GABA sensitivity and provide further support for the regional heterogeneity of chronic diazepam effects.

Full Text

Duke Authors

Cited Authors

  • Heninger, C; Saito, N; Tallman, JF; Garrett, KM; Vitek, MP; Duman, RS; Gallager, DW

Published Date

  • 1990

Published In

Volume / Issue

  • 2 / 2

Start / End Page

  • 101 - 107

PubMed ID

  • 1964063

Pubmed Central ID

  • 1964063

International Standard Serial Number (ISSN)

  • 0895-8696

Language

  • eng

Conference Location

  • United States