Nicotine Sensitization and Analysis of Brain-Derived Neurotrophic Factor in Adolescent β-Arrestin-2 Knockout Mice
Nicotine Sensitization and Analysis of Brain-Derived Neurotrophic Factor in Adolescent β-Arrestin-2 Knockout Mice
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DOI：
10.1002/syn.20625
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发表时间：
2009-06-01
期刊：
影响因子：
2.3
通讯作者：
Brown, Russell W.
中科院分区：
文献类型：
--
作者：
Correll, Jennifer A.;Noel, Daniel M.;Brown, Russell W.
在青春期β-arrestin-2敲除（β A-2 KO）和野生型（WT）小鼠中分析尼古丁致敏和脑源性神经营养因子（BDNF）水平。β-抑制蛋白-2蛋白已被证明在G蛋白水解和受体内化中是重要的。连续7天（实验1）或14天（实验2），在将4 - 5周龄青春期β A-2 KO和WT C57/B16小鼠置于运动竞技场前10分钟给予尼古丁（0.5 mg/kg游离碱）或生理盐水。致敏完成后7天给予尼古丁激发。在实验1中，给予尼古丁或生理盐水的β A-2 KO小鼠和给予尼古丁的WT小鼠在试验早期表现出显著的活动减退，给予尼古丁的WT和β A-2 KO小鼠均未表现出致敏作用。在尼古丁激发时，与所有组相比，给予尼古丁的WT小鼠表现出显著更高的活性水平，并且与所有组相比，同一组表现出显著更高的脑源性BDNF水平。在实验2中，与WT小鼠相比，β A-2 KO小鼠再次活动减退，而给予尼古丁的WT小鼠在初始测试期间表现出显著的活动减退，并且在测试后期与所有其他组相比表现出显著更高的活动水平。在尼古丁激发时，与所有组相比，接受尼古丁的WT小鼠表现出活性显著增加，并且与所有组相比，表现出脑源性BDNF增加。这些结果表明，β-arrestin-2蛋白在尼古丁敏化的诱导和表达以及尼古丁对脑源性BDNF的影响中是重要的。Synapse 63：510-519，2009. (C)Wwiley-Liss，Inc.
Nicotine sensitization and levels of brain-derived neurotrophic factor (BDNF) were analyzed in adolescent beta-arrestin-2 knockout (beta A-2 KO) and wild type (WT) mice. The beta-arrestin-2 protein has been shown to be important in G-protein hydrolysis and receptor internalization. Four- to five-week-old adolescent beta A-2 KO and WT C57/B16 mice were administered either nicotine (0.5 mg/kg free base) or saline 10 min before being placed into a locomotor arena on each of 7 (Experiment 1) or 14 (Experiment 2) consecutive days. A nicotine challenge was given 7 days after sensitization was complete. In Experiment 1, beta A-2 KO mice administered nicotine or saline and WT mice administered nicotine demonstrated significant hypoactivity during early in testing, and neither WT nor beta A-2 KO mice administered nicotine demonstrated sensitization. On the nicotine challenge, WT mice administered nicotine demonstrated significantly higher activity levels compared to all groups, and this same group demonstrated significantly higher levels of accumbal BDNF compared to all groups. In Experiment 2, beta A-2 KO mice were again hypoactive compared to WT mice, whereas WT mice administered nicotine demonstrated significant hypoactivity during initial testing and significantly higher levels of activity compared to all other groups late in testing. On the nicotine challenge, WT mice that received nicotine demonstrated a significant increase in activity compared to all groups, and showed increased accumbal BDNF compared to all groups. These results show that the beta-arrestin-2 protein is important in induction and expression of nicotine sensitization as well as nicotine's effects on accumbal BDNF. Synapse 63:510-519, 2009. (C) 2009 Wwiley-Liss, Inc.