Affiliation:
1. Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK
Abstract
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 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 GABAA receptors is the mechanism responsible for the development of tolerance to, or dependence on, benzodiazepines.
Subject
Pharmacology (medical),Psychiatry and Mental health,Pharmacology
Reference36 articles.
1. ?-Aminobutyric AcidAReceptor Heterogeneity Is Increased by Alternative Splicing of a Novel ?-Subunit Gene Transcript
2. Inhibition of acetylcholine receptor assembly by activity in primary cultures of embryonic rat muscle cells.
3. Gallager D.W., Heninger C., Wilson M.A. (1988) Chronic benzodiazepine agonist exposure and its consequences to GABA-benzodiazepine interactions. In Barnard E, Costa E (eds), The allosteric modulation of amino acid receptors and its therapeutic implications . Raven Press, New York, pp.91-108
4. Chronic benzodiazepine treatment decreases postsynaptic GABA sensitivity
Cited by
20 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献