PI-3K信号通路在吗啡依赖纳洛酮激发戒断反应中的作用

The Role of Phosphoinositide 3-kinase Pathway in Morphine Dependent and Naloxone-precipitated Withdrawal Response

目的:研究PI-3K信号通路在吗啡依赖纳洛酮激发戒断反应中的作用。方法:在小鼠急性和慢性吗啡依赖和戒断模型上,采用鞘内和脑室内注射PI-3K抑制剂对吗啡依赖小鼠纳洛酮催促戒断反应的影响,探讨神经元PI-3K信号通路吗啡依赖和戒断过程中的作用。结果:鞘内预先注射PI-3K信号通路抑制剂LY294002及W ortm an in能明显加重急性和慢性吗啡依赖小鼠纳洛酮激发戒断反应。脑室内预先注射PI-3K信号通路抑制剂LY294002及W ort-m an in也明显加重急性和慢性吗啡依赖小鼠纳洛酮激发戒断反应。结论:脊髓和脊髓上中枢神经元PI-3K信号通路均参与吗啡依赖的形成及戒断反应的表达。

Objective： To investigate the roles of the PI3K in morphine dependent and naloxone-precipitated withdrawal response. Methods： With the acute and chronic morphine dependent mouse model, morphine withdrawal syndrome was precipitated by an injection of naloxone. DMSO or PI3K inhibitor （LY294002 or Wortmanin） was intrathecally or intracerebroventricular injected 10 rain before the administration of naloxone. The jump response of mice during the first 15 rain after injection of naloxone were observed. Results： Intrathecally or intracerebroventricular Phosphoinositide 3-kinase （PI3K） inhibitor （LY294002 or Wortmanin） both aggravated morphine dependent and naloxone-precipitated withdrawal response in mice. Conclusion： Both spinal and supraspinal neuronal Phosphoinositide 3-kinase （PI3K） pathway played important role in morphine dependent and naloxone-precipitated withdrawal response in mice.