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Journal of Psychopharmacology, Vol. 6, No. 3, 364-369 (1992)
DOI: 10.1177/026988119200600304

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

Michael C. O'Donovan

Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK

Paul R. Buckland

Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK

Peter McGuffin

Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK

The regulation of the subunit composition of GABAA 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 GABAA ß1, 2, 3 and {gamma}2 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 ß-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 ß or {gamma}2 subunit composition of GABAA receptors is the mechanism responsible for the development of tolerance to, or dependence on, benzodiazepines.

Key Words: benzodiazepines • tolerance • GABAA receptor • mRNA levels


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