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Updated: May 25, 2026
GABA-activated Single-channel and Tonic Currents in Rat Brain Slices
Published on: July 17, 2011
Levels of GABAa receptor subunit mRNA in rat brain following flurazepam treatment
M C O'Donovan1, P R Buckland, P McGuffin
1Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK.
Abstract:
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.
Insights
Benzodiazepine tolerance is not caused by changes in GABA(A) receptor subunit mRNA levels. This study found no alterations in key subunit messenger RNA in rats treated with flurazepam, refuting a common hypothesis.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Benzodiazepines are widely prescribed for anxiety and insomnia.
- Tolerance to benzodiazepines can develop with chronic use, necessitating higher doses.
- The role of GABA(A) receptor subunit composition in this tolerance is debated.
Purpose of the Study:
- To investigate if changes in GABA(A) receptor subunit mRNA levels contribute to benzodiazepine tolerance.
- To examine the expression of GABA(A) receptor β1, β2, β3, and γ2 subunits during chronic flurazepam administration.
Main Methods:
- Male Wistar rats received daily injections of flurazepam or vehicle for up to 32 days.
- Brain RNA was isolated from treated and control rats.
- Messenger RNA (mRNA) levels for specific GABA(A) receptor subunits were quantified using RT-PCR relative to a β-actin standard.
Main Results:
- No significant changes in the mRNA levels of GABA(A) receptor β1, β2, β3, or γ2 subunits were observed in rats treated with flurazepam compared to controls.
- These mRNA levels remained stable throughout the 32-day treatment period.
Conclusions:
- The findings do not support the hypothesis that alterations in GABA(A) receptor subunit composition, specifically at the mRNA level, underlie the development of tolerance to or dependence on benzodiazepines.
- Alternative mechanisms may be responsible for benzodiazepine tolerance and dependence.
