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以递增剂量吗啡ｓｃ，使小鼠产生对吗啡的躯体依赖，观察脑组织ｃＧＭＰ水平、ＰＤＥ和ｓＧＣ的活性变化及ＰＫＡ对其磷酸化调节。结果表明，（１）小脑、纹状体、海马及大脑皮质ｃＧＭＰ含量显著降低；（２）在小脑、海马中ｓＧＣ活性明显降低，ＰＤＥ活性无明显变化，在纹状体及大脑皮质中均明显升高，且体外磷酸化水平也均明显下降，ＰＫＡ抑制剂可抑制此变化；（３）纳洛酮拮抗组未见上述变化。结果提示，吗啡依赖小鼠脑组织ｃＧＭＰ水平普遍降低，在小脑和海马可能因ｓＧＣ活性下降引起，在纹状体及大脑皮质可能因ＰＤＥ活性升高所致。
Morphological dependence on morphine was observed in mice treated with increasing doses of morphine sc. The level of cGMP, the activity of PDE and sGC in brain and the phosphorylation of PKA were observed. The results showed that: (1) The content of cGMP in cerebellum, striatum, hippocampus and cerebral cortex decreased significantly; (2) The activity of sGC in cerebellum and hippocampus was significantly decreased, while the activity of PDE did not change obviously, which was obvious in striatum and cerebral cortex And phosphorylation levels in vitro were also significantly decreased, PKA inhibitors can inhibit this change; (3) naloxone antagonist group did not see the above changes. The results suggest that the level of cGMP in the brain of morphine-dependent mice is generally decreased, which may be caused by the decrease of sGC activity in the cerebellum and hippocampus, and the increase of PDE activity in the striatum and cerebral cortex.