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 |
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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. |
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作者姓名: | 刘惠芬 周文华 唐甩恩 赖苗军 刘胜 陈为升 杨国栋 |
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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) |
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基金项目: | 国家重大基础研究项目(2003CB515404),国家自然科学基金(30100051) |
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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。
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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 |
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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. |
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Keywords: | Morphine Withdrawal Muscarinic acetylcholine receptor GDNF Fos |
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