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鞘内注射M受体和GDNF反义寡脱氧核苷酸抑制吗啡戒断大鼠蓝斑c-Fos表达
引用本文:刘惠芬,周文华,唐甩恩,赖苗军,刘胜,陈为升,杨国栋.鞘内注射M受体和GDNF反义寡脱氧核苷酸抑制吗啡戒断大鼠蓝斑c-Fos表达[J].分子细胞生物学报,2005,38(3):211-218.
作者姓名:刘惠芬  周文华  唐甩恩  赖苗军  刘胜  陈为升  杨国栋
作者单位:刘惠芬(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)       周文华(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)       唐甩恩(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)       赖苗军(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)       刘胜(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)       陈为升(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)       杨国栋(宁波微循环与莨菪类药研究所,宁波戒毒研究中心,宁波,315010)
基金项目:国家重大基础研究项目(2003CB515404),国家自然科学基金(30100051)
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。

关 键 词:吗啡  戒断  毒蕈碱型乙酰胆碱受体  GDNF  Fos
修稿时间:2004年7月7日

INTRATHECAL INJECTION OF MUSCARINIC RECEPTORS OR GDNF ANTISENSE OLIGONUCLEOTIDES INHIBITS THE INCREASE OF C-FOS EXPRESSION IN LOCUS COERULEUS OF MORPHINE-WITHDRAWAL RATS
Abstract: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.
Keywords:Morphine  Withdrawal  Muscarinic acetylcholine receptor  GDNF  Fos
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