Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKCγ null mutant mice
Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKCγ null mutant mice
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DOI：
10.1016/s0091-3057(01)00510-x
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发表时间：
2001-05-01
影响因子：
3.6
通讯作者：
Wehner, JM
中科院分区：
文献类型：
--
作者：
Bowers, BJ;Elliott, KJ;Wehner, JM
在PKC γ无效突变小鼠中进行的乙醇效应试验表明，PKC γ在对乙醇诱导的镇静、低温和GABA（A）受体功能的初始敏感性中起作用，并影响介导焦虑的神经化学途径。本研究旨在评估先前在这些小鼠中观察到的对乙醇的敏感性降低是否普遍适用于乙醇的抗焦虑作用。在高架十字迷宫、黑/白色箱和镜室中，在乙醇（0、1.0、1.25、1.5 g/kg）或氟硝西泮（FNZ）（0、0.015、0.03、0.06 mg/kg）后测试PKC γ无效突变小鼠和野生型对照。结果表明，虽然这两种基因型表现出抗焦虑反应，乙醇在高架十字迷宫，无效突变小鼠的敏感性低于野生型对照小鼠，然而，在黑/白色框，PKC γ无效突变体比对照组更敏感的抗焦虑作用FNZ。无论是乙醇，也不FNZ产生抗焦虑反应，在镜像室的基因型。这些结果表明，PKC γ差异介导的抗焦虑反应，乙醇和FNZ，这种关系相互作用与每种药物的疗效，减少焦虑相关的行为，具体到每三个迷宫。(C)2001 Elsevier Science Inc. All rights reserved.
Tests of ethanol effects in PKC gamma null mutant mice have indicated that PKC gamma plays a role in initial sensitivity to ethanol-induced sedation, hypothermia, and GABA(A) receptor function and impacts neurochemical pathways mediating anxiety. The present study was undertaken to evaluate whether the decreased sensitivity to ethanol previously observed in these mice generalized to the anxiolytic effects of ethanol. PKC gamma null mutant mice and wild-type controls were tested in the elevated-plus maze, the black/white box, and the mirrored chamber after ethanol (0, 1.0, 1.25, 1.5 g/kg) or flunitrazepam (FNZ) (0, 0.015, 0.03, 0.06 mg/kg). Results indicated that although both genotypes exhibited anxiolytic responses to ethanol in the elevated plus-maze, null mutant mice were less sensitive than wild-type control mice; however, in the black/white box, PKC gamma null mutants were more sensitive than controls to the anxiolytic effects of FNZ. Neither ethanol nor FNZ produced anxiolytic responses in the mirrored chamber for either genotype. These results suggest that PKC gamma differentially mediates anxiolytic responses to ethanol and FNZ and that this relationship interacts with each drug's efficacy in reducing anxiety-related behaviors specific to each of the three mazes. (C) 2001 Elsevier Science Inc. All rights reserved.