Liu Qiaofeng, Wang Xin, Liu Yanyou, Lu Rui, Yuan Quan, Yang Bin, Zhou Jiang, Wang Yuhui, Wang Zhengrong
Key Laboratory of Chronobiology, School of Huaxi Preclinical Medicine and Forensic Medicine, Sichuan University, Chengdu, China.
Neurol Res. 2011 Jan;33(1):56-62. doi: 10.1179/016164110X12714125204236. Epub 2010 May 18.
We previously demonstrated that receptor for activated C kinase 1 (RACK1) inhibited phosphorylated extracellular signal-regulated kinase (p-ERK) during morphine reward in mice. In the present study, we examined the role of Src in regulating the inhibition of p-ERK in the brain following RACK1 over-expression during morphine reward.
Mice were subcutaneously injected with morphine on days 2, 4, 6, and 8 after pre-test (day 1), and saline was delivered the following day. After mice showed place preference, RACK1 over-expression plasmid was administered by intraventricular injection 20 minutes after morphine injection on days 11 and 13. Conditioned place preference (CPP) was measured on days 14, 15, 19, and 20.
Chronic morphine injection increased Src and p-ERK expression in cortex and hippocampus, and mice exhibited increased place preference. Intraventricular administration of RACK1 reduced Src and p-ERK levels in cortex and hippocampus, as well as morphine reward. At 7 days of final RACK1 administration, the effects of RACK1 on Src and p-ERK disappeared, and morphine place preference was restored.
We demonstrated that RACK1 acts on ERK activation via Src in morphine reward in mice.
我们之前证明，在小鼠吗啡奖赏过程中，活化C激酶1受体（RACK1）可抑制磷酸化细胞外信号调节激酶（p-ERK）。在本研究中，我们研究了Src在吗啡奖赏过程中RACK1过表达后脑内p-ERK抑制调节中的作用。
在预试验（第1天）后的第2、4、6和8天，给小鼠皮下注射吗啡，次日注射生理盐水。在小鼠表现出位置偏爱后，于第11和13天在注射吗啡20分钟后通过脑室内注射给予RACK1过表达质粒。在第14、15、19和20天测量条件性位置偏爱（CPP）。
慢性吗啡注射增加了皮质和海马中Src和p-ERK的表达，且小鼠表现出增强的位置偏爱。脑室内给予RACK1可降低皮质和海马中Src和p-ERK水平以及吗啡奖赏。在最后一次给予RACK1 7天后，RACK1对Src和p-ERK的作用消失，吗啡位置偏爱恢复。
我们证明，在小鼠吗啡奖赏过程中，RACK1通过Src作用于ERK激活。
