吗啡依赖与戒断大鼠脑组织μ阿片受体的变化

CHANGES OF μ OPIOID RECEPTOR IN BRAIN REGIONS OF MORPHINE DEPENDENT AND ABSTINENT RATS

目的 :用光学放射自显影术对吗啡依赖与戒断大鼠脑组织 μ阿片受体进行定位和定量研究。方法 :30只SD大鼠随机分为吗啡依赖组、吗啡戒断组和生理盐水对照组 ,每组 10只。依赖组和戒断组大鼠以腹腔注射吗啡的方法建立吗啡依赖模型 ,戒断组在依赖后腹腔注射纳洛酮 5mg/kg诱导戒断症状 ,对照组注射生理盐水。取大鼠不同脑区 (包括额叶皮质、海马、纹状体、丘脑、下丘脑 )进行光学放射自显影研究 ,分析大鼠依赖及戒断前后 μ阿片受体数目及分布的改变。结果 :(1)依赖组大鼠与对照组大鼠相比 ,额叶皮质、海马、纹状体、丘脑、下丘脑的 μ受体特异性结合密度发生非常显著下降 (P <0 .0 1) ;(2 )戒断组大鼠与吗啡依赖组比较 ,额叶皮质、丘脑、海马、纹状体、下丘脑的 μ受体特异性结合密度发生了显著的上调 (P <0 .0 5或 0 .0 1)。但除下丘脑外 (P >0 .0 5 ) ,其余脑区的μ受体特异性结合密度仍非常显著地低于正常水平 (P <0 .0 1)。结论 :实验结果表明大鼠不同脑区在吗啡依赖过程中 μ阿片受体出现明显下调 ,予纳洛酮催促戒断 ,μ阿片受体较依赖组大鼠有显著回升 ,但仍显著低于正常组水平 ,这可能是阿片类依赖和戒断的重要神经生物学机制之一。

Objective: To study the changes of μ opioid receptor in brain regions of morphine dependent and abstinent rats by light microscopy autoradiography. Methods: Thirty SD rats were divided randomly into three groups (n=10). The rats in dependent group and abstinent group were administered with morphine by intraperitoneal injection till morphine dependent models were founded. The rats in abstinent group were injected with naloxone 5 mg/kg to induce withdrawl syndromes, the rats in control group were injected with saline. All rats were sacrificed by decapitation 24 h after the injection. The coronal sections of discrete brain regions (frontal cortex, hippocampus, striatum, thalamus, hypothalamus) were cut. The localization and density of μ opioid receptor in all three groups were measured by light microscopy autoradiography. Results: (1) In morphine dependent group, the density of μ opioid receptor in frontal cortex, hippocampus, striatum, thalamus and hypothalamus were significantly lower than those in control group ( P <0.01). (2) In morphine abstinent group, the density of μ opioid receptor in frontal cortex, hippocampus, striatum, thalamus, hypothalamus were significantly higher than those in dependent group ( P <0.05 or 0.01). However, the density of μ opioid receptor in frontal cortex, hippocampus, striatum, thalamus ,except in hypothalamus ( P >0.05), were still significantly lower than those in control group ( P <0.01). Conclusion: Morphine dependence can lower the level of μ opioid receptor in rat brain, and after morphine abstinence by naloxone these changes are difficult to recover in short term, which may be involved in the neurobiological mechaisms of opioid dependence and abstinence.