NDLI: GABA$_{A}$-R α4 Subunits are Required for the Low Dose Locomotor Stimulatory Effect of Alphaxalone, But Not for Several Other Behavioral Responses to Alphaxalone, Etomidate or Propofol

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GABA$_{A}$-R α4 Subunits are Required for the Low Dose Locomotor Stimulatory Effect of Alphaxalone, But Not for Several Other Behavioral Responses to Alphaxalone, Etomidate or Propofol

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GABA$_{A}$-R α4 Subunits are Required for the Low Dose Locomotor Stimulatory Effect of Alphaxalone, But Not for Several Other Behavioral Responses to Alphaxalone, Etomidate or Propofol

Content Provider	Springer Nature Link
Author	Iyer, Sangeetha V. Chandra, Dave Homanics, Gregg E.
Copyright Year	2013
Abstract	γ-Aminobutyric acid type A receptors (GABA$_{A}$-Rs) 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 GABA$_{A}$-R subtypes involved in the mechanism of action of these three drugs. Here, we investigated the role of α4-subunit containing GABA$_{A}$-Rs 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 subunit-containing GABA$_{A}$-Rs 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.
Starting Page	1048
Ending Page	1056
Page Count	9
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	39
Issue Number	6
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2013-09-24
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	γ-Aminobutyric acid type A receptors Knockout mice Anesthetics Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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GABA$_{A}$-R α4 Subunits are Required for the Low Dose Locomotor Stimulatory Effect of Alphaxalone, But Not for Several Other Behavioral Responses to Alphaxalone, Etomidate or Propofol

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GABA$_{A}$-R α4 Subunits are Required for the Low Dose Locomotor Stimulatory Effect of Alphaxalone, But Not for Several Other Behavioral Responses to Alphaxalone, Etomidate or Propofol