Behavioral Characterization of β-Arrestin 1 Knockout Mice in Anxiety-Like and Alcohol Behaviors.
Behavioral Characterization of β-Arrestin 1 Knockout Mice in Anxiety-Like and Alcohol Behaviors.
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β-Arrestin 1 敲除小鼠在焦虑样和酒精行为中的行为特征。
DOI：
10.3389/fnbeh.2018.00054
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发表时间：
2018
影响因子：
3
通讯作者：
van Rijn RM
中科院分区：
文献类型：
--
作者：
Robins MT;Chiang T;Berry JN;Ko MJ;Ha JE;van Rijn RM
β-arrestin 1和2是高表达的蛋白，参与G蛋白偶联受体信号的脱敏，G蛋白偶联受体信号也调节多种细胞内信号通路。基因敲除(KO)研究表明，这两种异构体对基线和药物诱导行为的影响不是同源的；然而，与β-arrestin 2相比，β-arrestin 1在中枢神经系统中的作用研究较少。在这里，我们研究了全局β-arrestin 1 KO如何影响雄性和雌性C57BL/6小鼠的焦虑样行为和酒精相关行为。我们观察到，与野生型(WT)或杂合子(HET)小鼠相比，β-arrestin 1KO动物的基线运动活动增加，并存在性别效应。KO雄性小鼠在明/暗转换测试中不那么焦虑，尽管这种影响可能被增加的运动活动所混淆。不同基因型和性别之间的蔗糖摄入量没有差异。雌性β-arrestin 1KO小鼠在有限的4小时饮酒、两瓶选择、黑暗中饮酒的模型中，比雌性HET小鼠摄入更多10%的酒精。在20%酒精狂欢的通道模型中，雌性KO动物比HET和WT雌性动物摄入更多的酒精。在两种饮酒模式中都观察到了显著的性别效应，相对于体重，雌性小鼠比雄性小鼠消费了更多的酒精。β-arrestin 1KO小鼠对潜伏期翻正反射丧失(LOR)的敏感性增加，尽管LORR的持续时间没有观察到差异。总体而言，我们的努力表明，β-arrestin 1可能对女性增加饮酒和两性多动具有保护作用。
β-Arrestin 1 and 2 are highly expressed proteins involved in the desensitization of G protein-coupled receptor signaling which also regulate a variety of intracellular signaling pathways. Gene knockout (KO) studies suggest that the two isoforms are not homologous in their effects on baseline and drug-induced behavior; yet, the role of β-arrestin 1 in the central nervous system has been less investigated compared to β-arrestin 2. Here, we investigate how global β-arrestin 1 KO affects anxiety-like and alcohol-related behaviors in male and female C57BL/6 mice. We observed increased baseline locomotor activity in β-arrestin 1 KO animals compared with wild-type (WT) or heterozygous (HET) mice with a sex effect. KO male mice were less anxious in a light/dark transition test, although this effect may have been confounded by increased locomotor activity. No differences in sucrose intake were observed between genotypes or sexes. Female β-arrestin 1 KO mice consumed more 10% alcohol than HET females in a limited 4-h access, two-bottle choice, drinking-in-the-dark model. In a 20% alcohol binge-like access model, female KO animals consumed significantly more alcohol than HET and WT females. A significant sex effect was observed in both alcohol consumption models, with female mice consuming greater amounts of alcohol than males relative to body weight. Increased sensitivity to latency to loss of righting reflex (LORR) was observed in β-arrestin 1 KO mice although no differences were observed in duration of LORR. Overall, our efforts suggest that β-arrestin 1 may be protective against increased alcohol consumption in females and hyperactivity in both sexes.
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