摘要
应用免疫组化方法观察鞘内注射毒蕈碱型乙酰胆碱(muscarinic acetylcholine receptor,M) 受体和胶质细胞源性神经营养因子(glial cell derived neurotrophic factor,GDNF)反义寡脱氧核苷酸对吗啡戒断大鼠蓝斑(locus coeruleus,LC)区内Fos表达的影响。结果显示,鞘内注射M_2受体和GDNF反义寡脱氧核苷酸明显减少大鼠吗啡戒断症状评分值(n=6,P<0.05)。正常大鼠LC区神经元Fos基础表达较低,吗啡依赖大鼠LC区神经元Fos表达增加,吗啡依赖大鼠纳酪酮(4mg/Kg,ip)催促戒断后,Fos表达进一步增加;鞘内注射M_2受体和GDNF反义寡脱氧核苷酸处理后均减少吗啡戒断大鼠LC区神经元Fos表达(n=5,P<0.05)。而鞘内注射M_1受体反义寡脱氧核苷酸处理组LC 区神经元Fos表达较吗啡戒断组没有显著差异(n=5,P>O.05)。结果提示:脊髓M_2受体调节吗啡戒断时LC区的神经元激活,而这种神经上行性激活涉及神经元与胶质细胞之间的适应性调节。
The antisense approach and immunohistochemistry were used to study the effects of different muscarinic receptor (M) subtypes and glial cell derived neurotrophic factor (GDNF) on the scores of morphine-withdrawal syndrome and the expression of c-Fos in locus coeruleus (LC). Intrathecal injection of M_2 receptor antisense oligonucleotides (M_2AS-oligo) or GDNF antisense oligonucleotides (GDNFAS-oligo) decreased the scores of morphine withdrawal syndrome. The ex- pression of c-Fos positive neurons in the LC increased in morphine-dependent rats and increased to a greater extent after the injection of naloxone (4mg/kg, ip) in morphine dependent rats. In- trathecal injection of M_2AS-oligo or GDNFAS-oligo inhibited the increase of c-Fos expression in LC during morphine withdrawal, but there was no effect in case of M_1AS-oligo. The results suggest that M_2 receptor of spinal cord mediates the neural activation of LC during morphine withdrawal. And the interaction between neurons and glial cells may be involved in the ascending activation process.
出处
《实验生物学报》
CSCD
北大核心
2005年第3期211-218,共8页
Acta Biologiae Experimentalis Sinica
基金
国家重大基础研究项目(2003CB515404)
国家自然科学基金(30100051)
