Role of the calcium/calmodulin-dependent protein kinase ii (CaMKII) in the morphine-induced pharmacological effects in the mouse
Role of the calcium/calmodulin-dependent protein kinase ii (CaMKII) in the morphine-induced pharmacological effects in the mouse
复制标题
DOI：
10.1016/j.neuroscience.2004.03.006
复制
发表时间：
2004-12
期刊：
影响因子：
3.3
通讯作者：
M. Narita;Y. Matsumura;S. Ozaki;Y. Ise;Y. Ise;Y. Yajima;Tsutomu Suzuki
中科院分区：
文献类型：
--
作者：
M. Narita;Y. Matsumura;S. Ozaki;Y. Ise;Y. Ise;Y. Yajima;Tsutomu Suzuki
钙/钙调蛋白依赖性蛋白激酶II（CaMKII）是激活信号通路的多功能蛋白激酶家族。本研究旨在确定CaMK Ⅱ是否在吗啡诱导的小鼠抗伤害感受、过度运动和奖赏效应的表达中发挥重要作用。用CaMKII抑制剂KN-93 i. c. v.预处理未能影响s.c.给药原型μ-阿片受体激动剂吗啡。相比之下，静脉注射KN-93预处理可显着减弱吗啡诱导的位置偏好。磷酸化CaMKII（p-CaMKII）的水平在边缘前脑，但不是在额叶皮层和下中脑，显着增加在吗啡条件小鼠，而在三个脑区从吗啡条件小鼠的CaMKII的水平没有改变。这种上调的p-CaMKII在边缘前脑从吗啡条件小鼠得到显着抑制i. c. v.预处理KN-93。这些结果提供的证据表明，在小鼠边缘前脑CaMK Ⅱ活性的增加可能有助于奖励效应，但不是抗伤害和hypermotortion，由吗啡诱导。
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a family of multifunctional protein kinases that activates signaling pathways. The present study was designed to ascertain whether CaMKII could play a substantial role in the expression of morphine-induced antinociception, hyperlocomotion and rewarding effect in the mouse. An i.c.v. pretreatment with a CaMKII inhibitor KN-93 failed to affect the antinociception and hyperlocomotion induced by s.c. administration of a prototype μ-opioid receptor agonist morphine. In contrast, the morphine-induced place preference was significantly attenuated by i.c.v. pretreatment with KN-93. The levels of phosphorylated-CaMKII (p-CaMKII) in the limbic forebrain, but not in the frontal cortex and the lower midbrain, were significantly increased in morphine-conditioned mice, whereas the levels of CaMKII in three brain regions obtained from morphine-conditioned mice were not changed. This up-regulation of p-CaMKII in the limbic forebrain obtained from morphine-conditioned mice was significantly inhibited by i.c.v. pretreatment with KN-93. These results provide evidence that the increase in CaMKII activity in the mouse limbic forebrain may contribute to the rewarding effect, but not the antinociception and the hyperlocomotion, induced by morphine.