The role of alpha 1 and alpha 5 subunit-containing GABAA receptors in motor impairment induced by benzodiazepines in rats

The role of alpha 1 and alpha 5 subunit-containing GABAA receptors in motor impairment induced by benzodiazepines in rats

Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma -aminobutyric acid A (GABAA) receptors containing alpha 1 and alpha 5 subunits contribute to these motor-impairing effects...

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Bibliographic Details
Published in:Behavioural pharmacology Vol. 23; no. 2; pp. 191 - 197
Main Authors: Milic, M, Divljakovic, J, Rallapalli, S, van Linn, ML, Timic, T, Cook, J M, Savic, M M
Format: Journal Article
Language:English
Published: 01-04-2012
Subjects:
Antagonists
Ataxia
Benzodiazepine
Coordination
Diazepam
Flumazenil
gamma -Aminobutyric acid A receptors
Muscle contraction
Muscles
Zolpidem
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Summary:Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma -aminobutyric acid A (GABAA) receptors containing alpha 1 and alpha 5 subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha 1-selective agonist zolpidem, as well as nonselective, alpha 1-subunit and alpha 5-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10 mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by ( beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha 1 GABAA receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas 05 GABAA receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia.
Bibliography:ObjectType-Article-2
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ISSN:0955-8810
DOI:10.1097/FBP.0b013e3283512c85