EFFECTS OF CONTINUOUS DIAZEPAM ADMINISTRATION ON GABA-A SUBUNIT MESSENGER-RNA IN RAT-BRAIN

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 α1 and β1 subunits of the GABAA receptor. Northern blots were hybridized with32P-labeled GABA α1 and β1 cDNA probes, and resulting bands were quantified by autoradiography and densitometry. Levels of α1 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 α1 mRNA in any of the brain regions. Levels of β1 mRNA were examined by Northern blot analysis and also by solution hybridization analysis using a32P-labeled riboprobe. Both methods showed that β1 mRNA was not significantly changed by chronic diazepam treatment. These results demonstrate a specific change in α1 subunit that is associated with a state of altered GABA sensitivity and provide further support for the regional heterogeneity of chronic diazepam effects. © 1990 Humana Press Inc.