Correll Jennifer A, Noel Daniel M, Sheppard A Brianna, Thompson Kimberly N, Li Yi, Yin Deling, Brown Russell W
Department of Psychology, East Tennessee State University, Johnson City, Tennessee 37614, USA.
Synapse. 2009 Jun;63(6):510-9. doi: 10.1002/syn.20625.
Nicotine sensitization and levels of brain-derived neurotrophic factor (BDNF) were analyzed in adolescent beta-arrestin-2 knockout (betaA-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 betaA-2 KO and WT C57/Bl6 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, betaA-2 KO mice administered nicotine or saline and WT mice administered nicotine demonstrated significant hypoactivity during early in testing, and neither WT nor betaA-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, betaA-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.
在青春期β-抑制蛋白2基因敲除（βA-2 KO）和野生型（WT）小鼠中分析了尼古丁致敏作用及脑源性神经营养因子（BDNF）水平。β-抑制蛋白2已被证明在G蛋白水解和受体内化过程中起重要作用。在连续7天（实验1）或14天（实验2）中的每一天，将4至5周龄的青春期βA-2 KO和WT C57/Bl6小鼠在放入运动场地前10分钟给予尼古丁（0.5mg/kg游离碱）或生理盐水。致敏完成7天后给予尼古丁激发试验。在实验1中，给予尼古丁或生理盐水的βA-2 KO小鼠以及给予尼古丁的WT小鼠在测试早期表现出明显的活动减少，给予尼古丁的WT小鼠和βA-2 KO小鼠均未表现出致敏作用。在尼古丁激发试验中，给予尼古丁的WT小鼠与所有组相比表现出明显更高的活动水平，并且该组与所有组相比伏隔核BDNF水平明显更高。在实验2中，与WT小鼠相比，βA-2 KO小鼠再次表现出活动减少，而给予尼古丁的WT小鼠在初始测试期间表现出明显的活动减少，在测试后期与所有其他组相比表现出明显更高的活动水平。在尼古丁激发试验中，接受尼古丁的WT小鼠与所有组相比活动显著增加，并且与所有组相比伏隔核BDNF增加。这些结果表明，β-抑制蛋白2在尼古丁致敏作用的诱导和表达以及尼古丁对伏隔核BDNF的影响中起重要作用。
