Fang F, Wang X, Wang Q, Liu J
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005.
Yao Xue Xue Bao. 1998 Nov;33(11):816-20.
By inducing morphine dependence in mice, changes in inositol phosphate contents, protein kinase C(PKC) activity in brain regions and effect of PKC inhibitor on the development of morphine dependence were investigated. It was found that: (1) IP(inositol phosphate) and IP3 (inositol trisphosphate) contents in striatum, IP in cerebral cortex and total inositol phosphates(IP + IP2 + IP3) in striatum and cerebral cortex were markedly higher than those of the control. But no similar changes in hippocampus and cerebellum were observed. (2) Cytosolic PKC activity was significantly increased in cerebellum and cerebral cortex but decreased in striatum. The membrane PKC activity was apparently enhanced in striatum but decreased in cerebellum and hippocampus. (3) PKC inhibitor was found to prevent the development of morphine dependence. (4) These changes described above were not observed in mice treated with naloxone 30 min prior to daily morphine injection. Our data indicate that the increase of inositol phosphate contents in striatum implied activation of phospholipase C, which might lead to PKC activation. This PKC activation may be involved in the development of morphine dependence.
通过诱导小鼠吗啡依赖，研究了脑区肌醇磷酸含量、蛋白激酶C（PKC）活性的变化以及PKC抑制剂对吗啡依赖形成的影响。结果发现：（1）纹状体中肌醇磷酸（IP）和肌醇三磷酸（IP3）含量、大脑皮质中IP以及纹状体和大脑皮质中总肌醇磷酸（IP + IP2 + IP3）均显著高于对照组。但海马和小脑中未观察到类似变化。（2）胞质PKC活性在小脑和大脑皮质中显著增加，而在纹状体中降低。膜PKC活性在纹状体中明显增强，而在小脑和海马中降低。（3）发现PKC抑制剂可阻止吗啡依赖的形成。（4）在每日注射吗啡前30分钟用纳洛酮处理的小鼠中未观察到上述变化。我们的数据表明，纹状体中肌醇磷酸含量的增加意味着磷脂酶C的激活，这可能导致PKC激活。这种PKC激活可能参与了吗啡依赖的形成。
