Changes in GABAA receptor properties in amygdala kindled animals: in vivo studies using [11C]flumazenil and positron emission tomography

Epilepsia
Lia C LiefaardRob A Voskuyl

Abstract

The purpose of the present investigation was to quantify alterations in GABA(A) receptor density in vivo in rats subjected to amygdala kindling. The GABA(A) receptor density was quantified by conducting a [(11)C]flumazenil (FMZ) positron emission tomography (PET) study according to the full saturation method, in which each animal received a single injection of FMZ to fully saturate the GABA(A) receptors. Subsequently, the concentration-time curves of FMZ in blood [using high-pressure liquid chromatography with UV detector (HPLC-UV) or high-performance liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS)] and brain (with PET-scanning) were analyzed by population modeling using a pharmacokinetic model, containing expressions to describe the time course of FMZ in blood and brain. The GABA(A) receptor density (B(max)) in kindled rats was decreased by 36% compared with controls. This is consistent with a reduction of 28% in electroencephalography (EEG) effect of midazolam in the same animal model, suggesting that a reduced number of GABA(A) receptors underlies the decreased efficacy of midazolam. Furthermore, receptor affinity (K(D)) was not changed, but the total volume of distribution in the brain (V(Br)), is incre...Continue Reading

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Citations

Jan 1, 2011·Epilepsy Research and Treatment·Martine M Mirrione, Stella E Tsirka
Mar 19, 2014·Zeitschrift für medizinische Physik·Claudia Kuntner
Jul 17, 2014·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Floris H P van VeldenMarc C Huisman
Feb 22, 2012·Neuroscience and Biobehavioral Reviews·Kanwar VirdeeJeffrey W Dalley
Jan 19, 2011·Neuroscience Research·Wang XiHong Zhang
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Jan 11, 2019·International Journal of Molecular Sciences·Sandesh D ReddyDoodipala Samba Reddy
Jan 6, 2016·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Syahir MansorFloris H P van Velden
Nov 13, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Stina SyvänenRob A Voskuyl

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