Bi-directional changes in the levels of messenger RNAs encoding γ-aminobutyric acidA receptor α subunits after flurazepam treatment

O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Buckland, Paul Robert, Spurlock, Gillian and McGuffin, Peter 1992. Bi-directional changes in the levels of messenger RNAs encoding γ-aminobutyric acidA receptor α subunits after flurazepam treatment. European Journal of Pharmacology: Molecular Pharmacology 226 (4) , pp. 335-341. 10.1016/0922-4106(92)90051-V

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Abstract

Changes in γ-aminobutyric acidA (GABAA) receptor function have been observed following chronic benzodiazepine administration. The molecular mechanisms responsible are unknown, but one possibility is that benzodiazepines induce alterations in the expression of genes which encode subunits of the GABAA receptor complex, resulting in changes in the receptor structure and function. We have investigated this hypothesis by evaluating the effect of flurazepam 40 mg/kg i.p. on brain levels of the mRNAs which encode the α1, α2, α3, α5, and α6 subunits of the GABAA receptor complex. Rats were treated with flurazepam or vehicle for up to 32 days. No changes were found in the levels of α1 and α2 mRNA. A rapid decrease was found in the level of α5 mRNA; α3 mRNA was increased by 4 days of treatment and this was followed by an increase in α6 levels. These results support the hypothesis that the alteration in GABAA receptor function after benzodiazepine administration results from changes in subunit gene expression. Furthermore, the predicted consequences of the pattern of mRNA changes we have observed suggest that altered gene expression may be important in the genesis of benzodiazepine tolerance.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Elsevier
ISSN:	0922-4106
Last Modified:	25 Oct 2022 09:11
URI:	https://orca.cardiff.ac.uk/id/eprint/57620

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