论文部分内容阅读
目的:探讨吗啡长期给药处理后大鼠不同脑区MAO-B活性及咪唑啉受体含量的变化。方法:用[~3H]咪唑克生配体结合试验测定咪唑啉受体含量,用高效液相色谱法测定MAO-B活性。结果:咪唑克生和吗啡能剂量依赖性地抑制大鼠脑匀浆MAO-B活性。咪唑啉受体的内源性配体胍丁胺既不影响MAO-B活性,也不影响咪唑克生及吗啡对MAO-B活性的抑制作用。吗啡连续给药16d后大鼠大脑、海马、丘脑、纹状体及小脑内MAO-B活性均显著下调(P<0.01)。纳洛酮及咪唑克生单次给药对吗啡依赖大鼠上述脑区MAO-B活性均没有进一步影响;胍丁胺伴随吗啡给药后能显著抑制吗啡降低MAO-B活性的作用。吗啡连续给药后大鼠皮层和小脑咪唑啉受体数量减少而亲和力上调(P<0.05)或P<0.01)。结论:MAO-B活性与吗啡依赖大鼠发生戒断综合征相关,但与胍丁胺对吗啡镇痛作用的影响无关;胍丁胺对吗啡药理作用的影响与其激活咪唑啉受体有关。
OBJECTIVE: To investigate the changes of MAO-B activity and imidazolinone receptor content in different brain regions of rats treated with morphine for a long time. Methods: The imidazoline receptors were determined by [~ 3H] imidadiazolium binding assay and the activity of MAO-B was determined by high performance liquid chromatography. RESULTS: Imidacloprid and morphine inhibited the MAO-B activity in rat brain homogenate in a dose-dependent manner. Agmatine, an endogenous ligand for the imidazolinium receptor, neither affects MAO-B activity nor inhibits MAO-B activity by imidazole and morphine. MAO-B activity in brain, hippocampus, thalamus, striatum and cerebellum of rats after morphine administration for 16 days was significantly decreased (P <0.01). The single administration of naloxone and midazolam had no further effect on MAO-B activity in brain regions of morphine-dependent rats. Agmatine with morphine significantly inhibited the activity of morphine to reduce MAO-B activity. After continuous administration of morphine, the number of cortisol and cerebellum imidazoline receptors decreased and the affinity was increased (P <0.05) or P <0.01). CONCLUSION: MAO-B activity is related to withdrawal syndrome in morphine-dependent rats but not to the effect of agmatine on morphine analgesia. The effect of agmatine on the pharmacological effects of morphine is related to the activation of imidazolinone receptors.