Behavioral modulation of neuronal calcium/calmodulin-dependent protein kinase II activity: Differential effects on nicotine-induced spinal and supraspinal antinociception in mice
Behavioral modulation of neuronal calcium/calmodulin-dependent protein kinase II activity: Differential effects on nicotine-induced spinal and supraspinal antinociception in mice
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DOI：
10.1016/j.bcp.2007.07.008
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发表时间：
2007-10-15
影响因子：
5.8
通讯作者：
Damaj, M. Imad
中科院分区：
文献类型：
--
作者：
Damaj, M. Imad
最近的研究表明，在尼古丁诱导的抗伤害感受中，钙离子依赖性机制，特别是钙/钙调蛋白依赖性蛋白激酶II（CaM激酶II）参与了甩尾试验。脊髓被认为是一个可能的网站，这种参与。本研究的目的是探讨这一假设，即在热板试验中，尼古丁诱导的抗伤害感受存在类似的机制，这种反应被认为是中枢介导的。为了评估这些机制，评估了静脉注射CaM激酶II抑制剂对静脉注射或皮下注射产生的抗伤害感受的影响尼古丁在两个测试中此外，尼古丁的镇痛作用在缺乏一半CaM激酶II（CaM激酶II杂合型）的小鼠中进行了测试，并将其与野生型小鼠进行了比较。我们的结果表明，尽管结构上不相关的CaM激酶II抑制剂以剂量相关的方式阻断了甩尾试验中尼古丁的作用，但它们未能阻断热板反应。此外，在CaM激酶II杂合子小鼠中，甩尾试验中全身性尼古丁的抗伤害效应显著降低，但热板试验中无此效应。这些观察结果表明，与甩尾反应相反，尼古丁诱导的抗伤害感受机制在热板试验中主要不是通过CaM激酶II依赖性机制介导的。(C)2007年爱思唯尔公司All rights reserved.
Recent studies have implicated the involvement of Ca2+-dependent mechanisms, in particular calcium/calmodulin-dependent protein kinase II (CaM kinase II) in nicotine-induced antinociception using the tail-flick test. The spinal cord was suggested as a possible site of this involvement. The present study was undertaken to investigate the hypothesis that similar mechanisms exist for nicotine-induced antinociception in the hot-plate test, a response thought to be centrally mediated. In order to assess these mechanisms, i.c.v. administered CaM kinase II inhibitors were evaluated for their effects on antinociception produced by either i.c.v. or s.c. administration of nicotine in both tests. in addition, nicotine's analgesic effects were tested in mice lacking half of their CaM kinase II (CaM kinase II heterozygous) and compare it to their wild-type counterparts. our results showed that although structurally unrelated CaM kinase II inhibitors blocked nicotine's effects in the tail-flick test in a dose-related manner, they failed to block the hot-plate responses. In addition, the antinociceptive effects of systemic nicotine in the tail-flick but not the hotplate test were significantly reduced in CaM kinase II heterozygous mice. These observations indicate that in contrast to the tail-flick response, the mechanism of nicotine-induced antinociception in the hot-plate test is not mediated primarily via CaM kinase II-dependent mechanisms at the supraspinal level. (C) 2007 Elsevier Inc. All rights reserved.