Levels of GABAa receptor subunit mRNA in rat brain following flurazepam treatment.

The regulation of the subunit composition of GABA(A) receptors may be a mechanism by which tolerance to the effects of benzodiazepines occurs. We have investigated this hypothesis by examining the levels of mRNA which codes for the GABA(A) β1, 2, 3 and γ2 subunits. Male Wistar rats were injected once daily with either flurazepam or vehicle, sacrificed after treatment regimes of up to 32 days and the brain RNA isolated. The levels of specific mRNAs encoding the receptor subunits were measured relative to a β-actin standard. No changes were found in the levels of these mRNAs at any time points. Our results lend no support to the hypothesis that alterations in the β or γ2 subunit composition of GABA(A) receptors is the mechanism responsible for the development of tolerance to, or dependence on, benzodiazepines.