The Research Of Enzymological Changes On Cerebral Regions Related To Mophine Dependence In Rats

Objective: To establish models of morphine dependent rats, observe the changes of adenylate cyclase(AC), guanylate cyclase(GC), monoamine oxidase(MAO) on cerebral regions related to morphine dependence in rats. Then investigate the relationship between the enzymological changes on seven cerebral regions related to morphine dependence and the mechanism of morphine dependence. And provide objective enzymological evidences for withdrawal therapy and drug exploitation. Method: Models of morphine dependent rats were established by back hypodermic injection and withdrawal symptoms were evaluated. On the foundation of localization by me methods of anatomy stereoscopic localization and hematoxylin and eosin staining(HE staining), used the technique of enzyme-histochemistry to detect the variations of AC, GC and MAO of special seven cerebral regions related to morphine dependence, which were frontalis cortex, lenticula, corpus amygdaloideun, substantia nigra, hippocampus, periaqueductal gray and locus coerleus of morphine dependent rats. The enzymological changes were observed by optical microscope. Assay changes of gray degree of these cerebral regions used the Image Analysis System. And the results were compared with those of control group. Used transmission electron microscope (TEM) to observe the location of these enzymes. Result: Rats of morphine dependent groups appeared conspicuous withdrawal symptoms, and withdrawal syndrome scores were significantly higher than that of control group. The major of enzymological changes of seven regions related to morphine dependence were as follow: compared with morphine dependent groups and control group, the contents of AC and GC are increase, but the contents of MAO are decrease. It has significant difference among these groups. Compared the four morphine-dependentgroups (1 week, 2 weeks, 4 weeks and 8 weeks ) with each other, the contents of AC, GC are significant difference between 1 week and 2 weeks, 4weeks, 8 weeeks; between 2 week and 4weeks, 8 weeeks. The contents of MAO has significant difference between the control group and the morphine-dependent groups. It is more notable between the control group and two morphine-dependent groups (that is 4 weeks and 8 weeks). The locations of products of AC and GC in sub-cellular structures is major in the mitochondrion, plasmalemma and the side near cytoplasm. The locations of products of MAO in sub-cellular structures is major in the extra-plasmalemma of mitochondrion. Conclusion : The models of morphine dependent rats are established by back hypodermic injection morphine. The enzymological changes of seven cerebral regions related to dependence are firstly observed. Result shows the contents of AC, GC are increase in these regions and the contents of MAO is decrease. The mechanism of morphine dependence close related to the increase of AC, GC and the decrease of MAO. The correlation of the mechanism of morphine dependence and up-regulation of AC/cAMP-PKA system, variation of NO-cGMP system, variation of MAO is discussed. It is a new development of this area.