[大鼠脑实质中脑脊液接触神经元的损伤抑制吗啡依赖和戒断的发展]

[The lesion of CSF contacting neurons in rat brain parenchyma inhibits the development of morphine dependence and withdrawal].

作者信息

Qin Cheng-Wei, Zhang Li-Cai, Zeng Yin-Ming

机构信息

Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou 221002, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 Aug;23(3):286-91.

PMID:21162265

Abstract

AIM

To investigate the effect of CSF contacting neurons (CSF-CNs) lesion in rat dorsal raphe nucleus (DRN) on the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord, and study the relationship between the distal CSF-CNs in rat brain parenchyma and the development of morphine dependence and withdrawal.

METHODS

Chemical lesion of neurons the injection of cholera toxin subunit B with horseradish peroxidase (CB-HRP) into one of the rats lateral ventricles, TMBST reaction, nNOS immunohistochemistry and Western blot were used in this study.

RESULTS

The withdrawal symptoms by the naloxone precipitated attenuated obviously after the lesion of CSF-CNs in rat DRN, scores of all signs were significantly decreased about 38% compared to that of withdrawal group without lesion (P < 0.05). The withdrawal symptoms scores of vehicle withdrawal group and side lesion withdrawal group were not changed significantly (P > 0.05). Neurons in the location of CSF-CNs concentrated in the rat brain slices of lesion group were damaged obviously, there were only few CB-HRP positive neurons around the lesion location. But the location and the quantity of the CB-HRP positive neurons in the brain slices of the group without lesion was stable relatively, and their appearance was very clear. After the lesion, the nNOS expression and the quantity of the nNOS positive neurons in dorsal horn of spinal cord decreased significantly compared to that of withdrawal group without lesion (P < 0.05), but it also increased significantly compared to that of normal group and dependence group (P < 0.01).

CONCLUSION

The lesion of distal CSF contacting neurons attenuated the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord. The distal CSF contacting neurons in rat brain parenchyma partly participated in the development of morphine dependence and naloxone precipitated withdrawal possibly by the modulation of NO (nitric oxide).

摘要

目的

研究大鼠中缝背核（DRN）中脑脊液接触神经元（CSF-CNs）损伤对纳洛酮诱发的吗啡戒断症状评分及脊髓背角nNOS表达的影响，探讨大鼠脑实质内远端CSF-CNs与吗啡依赖及戒断发展的关系。

方法

采用向大鼠侧脑室内注射霍乱毒素B亚基与辣根过氧化物酶（CB-HRP）进行神经元化学损伤、TMBST反应、nNOS免疫组化及蛋白质免疫印迹法。

结果

大鼠DRN中CSF-CNs损伤后，纳洛酮诱发的戒断症状明显减轻，与未损伤的戒断组相比，各项体征评分均显著降低约38%（P<0.05）。溶剂对照组和侧脑室损伤对照组的戒断症状评分无明显变化（P>0.05）。损伤组大鼠脑片CSF-CNs所在部位的神经元明显受损，损伤部位周围仅见少量CB-HRP阳性神经元。而未损伤组脑片CB-HRP阳性神经元的位置和数量相对稳定，形态清晰。损伤后，与未损伤的戒断组相比，脊髓背角nNOS表达及nNOS阳性神经元数量显著降低（P<0.05），但与正常组和依赖组相比也显著增加（P<0.01）。