GABAA-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.
GABAA-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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DOI：
10.1007/s11064-013-1148-3
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发表时间：
2014-06
影响因子：
4.4
通讯作者：
Homanics, Gregg E.
中科院分区：
文献类型：
--
作者：
Iyer, Sangeetha V.;Chandra, Dave;Homanics, Gregg E.
γ-氨基丁酸A型受体（GABAA-Rs）被认为是注射麻醉剂如丙泊酚、依托咪酯和神经甾体类药物阿法沙龙的主要分子靶点。许多研究试图了解这三种药物作用机制中涉及的特定GABAA-R亚型。本研究探讨了含α4亚基的GABAA-R在这些药物引起的神经行为反应中的作用。将α4亚基敲除（KO）小鼠的药物应答与野生型同窝对照进行比较。虽然依托咪酯和丙泊酚目前被用作可注射麻醉剂，但阿法沙龙属于具有麻醉作用的神经类固醇药物类别。使用开放场试验研究了依托咪酯和阿法沙龙的低剂量效应。分别使用旋转棒和翻正反射试验测定所有三种麻醉剂的中等和高剂量效应。与WT对照组相比，α4 KO小鼠中阿法沙龙的运动刺激作用显著降低。依托咪酯的低剂量镇静作用和任何药物的中/高剂量作用在基因型之间均无差异。这些结果表明，含α4亚基的GABAA-R是阿法沙龙低剂量运动刺激作用所必需的，但不是依托咪酯镇静作用或依托咪酯、丙泊酚或阿法沙龙对运动性共济失调和翻正反射丧失的中/高剂量作用所必需的。
γ-Aminobutyric acid type A receptors (GABAA-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 GABAA-R subtypes involved in the mechanism of action of these three drugs. Here, we investigated the role of α4-subunit containing GABAA-Rs in the neurobehavioral responses to these drugs. Drug responses in α4 subunit knockout (KO) mice were compared to wild type 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 GABAA-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.
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DOI：
10.1073/pnas.96.22.12905
发表时间：
1999-10-26
影响因子：
11.1
作者：
Mihalek, RM;Banerjee, PK;Homanics, GE
通讯作者：
Homanics, GE
DOI：
10.1073/pnas.89.15.6726
发表时间：
1992-08-01
影响因子：
11.1
作者：
FRITSCHY, JM;BENKE, D;MOHLER, H
通讯作者：
MOHLER, H
影响因子：
9.8
作者：
Fagerlund, M. Jonsson;Sjodin, J.;Dabrowski, M. A.
通讯作者：
Dabrowski, M. A.
DOI：
10.1111/j.1530-0277.2007.00563.x
发表时间：
2008-01-01
影响因子：
3.2
作者：
Chandra, Dev;Werner, David F.;Homanics, Gregg E.
通讯作者：
Homanics, Gregg E.
DOI：
10.1111/j.1530-0277.2007.00564.x
发表时间：
2008-01-01
影响因子：
3.2
作者：
Liang, Jing;Suryanarayanan, Asha;Spigelman, Igor
通讯作者：
Spigelman, Igor