脊髓阿片μ受体和NMDA受体在吗啡耐受过程中的变化

Changes of the spinal opioid μ receptors and NMDA receptors during the development of morphine tolerance

目的探讨脊髓阿片μ受体(μ-R)和NMDA受体(NMDA-R)数量在吗啡耐受过程中的变化,为进一步阐明吗啡耐受机制提供实验资料。方法建立慢性吗啡耐受大鼠模型,用免疫组织化学方法观察脊髓后角阿片μ-R和NMDA-R数量在吗啡耐受过程中的变化,并观察非竞争性NMDA-R拮抗剂MK-801对吗啡耐受过程中阿片μ-R和NMDA-R数量的影响。结果吗啡耐受过程中阿片μ-R数量减少(下调),NMDA-R数量增加(上调);MK-801可部分拮抗吗啡耐受,可以阻断吗啡耐受过程中NMDA-R数量的增加,但对μ-R数量的变化无影响。结论吗啡耐受的机制可能涉及μ-R的下调及NMDA-R的上调,MK-801可能通过抑制NMDA-R上调而具有部分抗吗啡耐受作用。

Objective To explore the quantitative changes of opioid μ receptors and NMDA receptors in spinal cord during the development of morphine tolerance, and to provide experimental data in order to find out the possible mechanism of morphine tolerance. Methods The chronic morphine tolerance mouse model was established. The quantitative changes of opioid μ receptors and NMDA receptors in lumbar spinal cord were observed by immunohistochemical ABC method. And the effects of the non-competitive NMDA antagonist （MK-801） on the quantity of opioid μ receptors and NMDA receptors during the development of morphine tolerance were observed. Result The quantity of the opioid μ receptors decreased, while the NMDA receptors increased during the development of morphine tolerance. MK-801 coadministrated with morphine could stop the development of morphine tolerance partly. MK-801 could block the increase of NMDA receptors, but had no effects on the quantity of opioid μ receptor during morphine tolerance. Conclusion Decrease in the opioid μ receptors and increase in the NMDA receptors may be involved in the mechanism of morphine tolerance. The effect of MK801 on morphine tolerance maybe associated with inhibiting the increase of NMDA receptors.