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Title of Journal: Neurochem Res

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Abbravation: Neurochemical Research

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Springer US

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DOI

10.1016/j.bcmd.2016.06.004

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1573-6903

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GABASubscriptA/SubscriptR α4 Subunits are Req

Authors: Sangeetha V Iyer Dave Chandra Gregg E Homanics
Publish Date: 2013/09/24
Volume: 39, Issue: 6, Pages: 1048-1056
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Abstract

γAminobutyric acid type A receptors GABAARs are considered to be the primary molecular targets of injectable anesthetics such as propofol etomidate and the neurosteriod alphaxalone A number of studies have sought to understand the specific GABAAR subtypes involved in the mechanism of action of these three drugs Here we investigated the role of α4subunit containing GABAARs in the neurobehavioral responses to these drugs Drug responses in α4 subunit knockout KO mice were compared to wild type WT littermate controls While etomidate and propofol are currently used as injectable anesthetics alphaxalone belongs to the class of neurosteroid drugs having anesthetic effects Low dose effects of etomidate and alphaxalone were studied using an open field assay The moderate and high dose effects of all three anesthetics were measured using the rotarod and loss of righting reflex assays respectively The locomotor stimulatory effect of alphaxalone was reduced significantly in α4 KO mice compared to WT controls Neither the low dose sedating effect of etomidate nor the moderate/high dose effect of any of the drugs differed between genotypes These results suggest that α4 subunitcontaining GABAARs are required for the low dose locomotor stimulatory effect of alphaxalone but are not required for the sedating effect of etomidate or the moderate/high dose effects of etomidate propofol or alphaxalone on motor ataxia and loss of righting reflex

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