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目的 观察急、慢性吗啡依赖时大鼠脑组织μ阿片受体（MOR）的调节及基因表达,探讨急、慢性吗啡依赖对MOR调节的差异性。方法40只SD大鼠随机分为对照组、急性依赖组、慢性依赖组、急性戒断组、慢性戒断组。急性依赖组大鼠背部皮下注射5mg/kg吗啡8次,间隔2h;慢性依赖组大鼠按小剂量递增法背部皮下注射吗啡,剂量为5、10、20、40、50、60mg·kg-1·d-1,每日3次（8:00,15:00,22:00）共6d。急、慢性戒断组在末次给药3h后腹腔注射5mg/kg纳洛酮,催促戒断24h。完成处置程序30min后,取脑组织,以3H-DAMGO进行Scatchard分析求出MOR的Bmax和Kd值,采用RT-PCR方法半定量测定MOR mRNA的表达。结果 1.急性吗啡依赖时大鼠脑组织MOR Bmax显著增高,亲和力显著下降,戒断后Bmax迅速恢复,而亲和力仍未能回到正常水平;吗啡慢性依赖时MOR的Bmax非常显著地下调,戒断后仍低于对照组,Kd值未发生明显改变。2.急性吗啡依赖使 MOR mRNA的表达非常显著地增高,戒断后迅速恢复,而吗啡慢性诱导无论依赖还是戒断状态,MOR mRNA的水平均明显低于正常。结论 急、慢性吗啡依赖对大鼠脑组织 MOR的调节方向不同,它们有着相类似的受体后机制。
Objective To observe the regulation of mu opioid receptor (MOR) and gene expression in the rat brain during acute and chronic morphine dependence, and to explore the difference of MOR between acute and chronic morphine dependence. Methods 40 SD rats were randomly divided into control group, acute dependence group, chronic dependence group, acute withdrawal group and chronic withdrawal group. Acute dependence group rats subcutaneous injection of 5mg / kg morphine 8 times, interval 2h; chronic dependence group rats by small dose escalation subcutaneous morphine, 5,10,20,40,50,60 mg · kg-1 · D-1, 3 times daily (8:00, 15:00, 22:00) for 6 days. The acute and chronic withdrawal groups were injected intraperitoneally with naloxone (5mg / kg) 3h after the last administration, and they were asked to quit for 24h. After 30 minutes of treatment, the brain tissues were harvested and the Bmax and Kd of MOR were determined by 3H-DAMGO Scatchard analysis. The mRNA expression of MOR was semi-quantitatively determined by RT-PCR. MORBmax was significantly increased in brain tissue of rats with acute morphine dependence, the affinity decreased significantly, Bmax recovered rapidly after abstinence, but the affinity still failed to return to normal level; Bmax of MOR was significantly down-regulated when chronic morphine dependence, Broken still lower than the control group, Kd value did not change significantly. Morphine dependence significantly increased the expression of MOR mRNA, and recovered rapidly after withdrawal. However, the MOR mRNA levels were significantly lower than those in chronic morphine dependent or abstinent. Conclusions The morphological changes of acute and chronic morphine dependence on MOR in brain tissue are different, and they have similar post-receptor mechanism.