کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2493644 1556652 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The influence of manipulations to alter ambient GABA concentrations on the hypnotic and immobilizing actions produced by sevoflurane, propofol, and midazolam
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
The influence of manipulations to alter ambient GABA concentrations on the hypnotic and immobilizing actions produced by sevoflurane, propofol, and midazolam
چکیده انگلیسی

Recent studies have suggested that extrasynaptic GABAA receptors, which contribute tonic conductance, are important targets for general anesthetics. We tested the hypothesis that manipulations designed to alter ambient GABA concentrations (tonic conductance) would affect hypnotic (as indicated by loss of righting reflex, LORR) and immobilizing (as indicated by loss of tail-pinch withdrawal reflex, LTWR) actions of sevoflurane, propofol, and midazolam. Two manipulations studied were 1) the genetic absence of glutamate decarboxylase (GAD) 65 gene (GAD65−/−), which purportedly reduced ambient GABA concentrations, and 2) the pharmacological manipulation of GABA uptake using GABA transporter inhibitor (NO-711). The influence of these manipulations on cellular and behavioral responses to the anesthetics was studied using behavioral and electrophysiological assays. HPLC revealed that GABA levels in GAD65−/− mice were reduced in the brain (76.7% of WT) and spinal cord (68.5% of WT). GAD65−/− mice showed a significant reduction in the duration of LORR and LTWR produced by propofol and midazolam, but not sevoflurane. NO-711 (3 mg/kg, ip) enhanced the duration of LORR and LTWR by propofol and midazolam, but not sevoflurane. Patch-clamp recordings revealed that sevoflurane (0.23 mM) slightly enhanced the amplitude of tonic GABA current in the frontal cortical neurons; however, these effects were not strong enough to alter discharge properties of cortical neurons. These results demonstrate that ambient GABA concentration is an important determinant of the hypnotic and immobilizing actions of propofol and midazolam in mice, whereas manipulations of ambient GABA concentrations minimally alter cellular and behavioral responses to sevoflurane.


► Ambient GABA is an important determinant of responses to propofol and midazolam.
► Ambient GABA minimally alters behavioral responses to sevoflurane.
► Sevoflurane (0.23 mM) minimally alters discharge properties of cortical neurons.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 61, Issues 1–2, July–August 2011, Pages 172–180
نویسندگان
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