脊髓或脑室注射胍丁胺对吗啡药理作用的影响  

Influence of Intracerebroventricular and Intrathecal Injection of Agmatine on Morphine Pharmacological Effects

作　　者：路新强[1] 苏瑞斌[2] 刘茵[2] 胡刚 李锦[2] 

机构地区：[1]南京医科大学药理学与生理学系,江苏南京210029 [2]中国人民解放军军事医学科学院毒物药物研究所,北京100850

出　　处：《解放军药学学报》2003年第5期324-327,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金 No .3 9970 845;北京市自然科学基金资助项目 No .7992 0 2 8

摘　　要：目的　分析胍丁胺调节吗啡药理作用的中枢部位。方法　在小鼠醋酸扭体、热辐射甩尾、物质依赖戒断等模型上 ,采用脑室和脊髓给药的方法 ,分析胍丁胺对吗啡药理作用的中枢部位。结果　在小鼠醋酸扭体实验中 ,胍丁胺对小鼠扭体次数具有明显的抑制作用 ,ED50 值为 1 0 .1mg·kg-1 。咪唑啉受体拮抗剂咪唑克生 ,每只小鼠 2 .0 μg脑室注射 ,完全对抗胍丁胺的上述镇痛作用 ,而等剂量的咪唑克生脊髓给药仅使胍丁胺的镇痛作用呈下降趋势 ,无统计学差别 (P >0 .0 5 ,n =1 0 )。在小鼠热辐射甩尾模型上 ,脑室或脊髓注射胍丁胺虽均能显著增强吗啡镇痛作用 ,但强度不同 ,胍丁胺脊髓注射能使吗啡镇痛ED50值减小 93.2 % ,而胍丁胺脑室注射仅使吗啡镇痛ED50 值减小 75 .0 %。在小鼠耐受和物质依赖模型上 ,胍丁胺脑室或脊髓注射也均能对抗吗啡耐受和依赖 ,以脑室给药作用为强。结论　胍丁胺镇痛、对抗吗啡耐受和物质依赖的主要作用部位在脊髓以上高位中枢 。Aim To analysis the sites of agmatine modulation on morphine pharmacological actions.Methods Mice acetic acid writhing test,mice heat radiation tail flick assay and mice abstinent jumping test were used to analysis the sites of agmatine modulation on morphine analgesia and tolerance to and dependence on morphine by intracerebroventricular (icv) and intrathecal (itt) injection.Results In mice acetic acid writhing test,subcutaneous administration of agmatine exhibited obvious analgesia,the value of ED 50 was 10.1mg·kg -1 .Idazoxan administrated by icv (2.0μg for each animal) could antagonize analgesia of agmatine completely,while same dose idazoxan given by itt only showed a tendency of inhibition on agmatine analgesia,and had no significant difference from that of control (P>0.05,n=10).In mice heat radiation tail flick assay,although agmatine administrated by icv or itt enhanced analgesia of morphine,the potency was quite different.Intrathecal agmatine decreased the ED 50 of morphine analgesia by 93.2%,while icv agmatine reduced the ED 50 only by 75.0%.In mice tolerance or substance dependence experimental models,both icv or itt injection of agmatine inhibited tolerance to and dependence on morphine,but intracerebroventricular injection of agmatine showed relatively stronger effect than intrthecal injection.Conclusion The site of the enhancing effect of agmatine on morphine analgesia is mainly located at spinal cord,while agmatine analgesia and inhibitory effects on tolerance to and dependence on morphine are mainly located at the brain.

关 键 词：胍丁胺 吗啡 药理作用 脊髓 

分 类 号：R971.2[医药卫生—药品]