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Gabra5 基因单倍型与苯二氮䓬类全激动剂氯氮䓬的行为特性相关。

Gabra5-gene haplotype block associated with behavioral properties of the full agonist benzodiazepine chlordiazepoxide.

机构信息

Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, 75651 Paris Cedex, France.

出版信息

Behav Brain Res. 2012 Aug 1;233(2):474-82. doi: 10.1016/j.bbr.2012.05.041. Epub 2012 Jun 4.

DOI:10.1016/j.bbr.2012.05.041
PMID:22677273
Abstract

The gabra5 gene is associated with pharmacological properties (myorelaxant, amnesic, anxiolytic) of benzodiazepines. It is tightly located (0.5 cM) close to the pink-eyed dilution (p) locus which encodes for fur color on mouse chromosome 7. We tested the putative role of the gabra5 gene in pharmacological properties of the full non specific agonist chlordiazepoxide (CDP), using behavioral and molecular approaches in mutated p/p mice and wild type F2 from crosses between two multiple markers inbred strain ABP/Le and C57BL/6By strain. From our results, using rotarod, light-dark box, elevated maze and radial arm maze tests, we demonstrate that p/p mice are more sensitive than WT to the sensory motor, anxiolytic and amnesic effect of CDP. This is associated with the presence of a haplotypic block on the murine chromosome 7 and with an up regulation of gabra5 mRNAs in hippocampi of p/p F2 mice.

摘要

gabra5 基因与苯二氮䓬类药物的药理学特性(肌松、健忘、抗焦虑)有关。它与编码小鼠 7 号染色体毛色的粉红色眼睛稀释(p)基因紧密相邻(0.5cM)。我们使用行为学和分子学方法,在突变的 p/p 小鼠和来自 ABP/Le 和 C57BL/6By 两个多标记近交系杂交的 F2 野生型中,测试了 gabra5 基因在全非特异性激动剂氯氮䓬(CDP)的药理学特性中的可能作用。通过转棒、明暗箱、高架迷宫和放射臂迷宫测试,我们证明 p/p 小鼠对 CDP 的感觉运动、抗焦虑和健忘作用比 WT 更敏感。这与鼠 7 号染色体上存在单倍型块以及 p/p F2 小鼠海马中 gabra5mRNA 的上调有关。

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