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M受体对吗啡戒断大鼠脊髓和脑干NMDA受体基因表达及中脑导水管周围灰质中谷氨酸释放的调节

刘惠芬, 周文华, 谢小虎, 曹君利, 顾钧, 杨国栋

宁波市微循环与莨菪类药研究所,宁波戒毒研究中心.浙江,宁波 315010

摘要

吗啡依赖大鼠脊髓NR_(1A)和NR_(2A) mRNA表达明显升高,而脑干中NR_(1A)和NR_(2A) mRNA表达没有显著变化;注射纳洛酮后1h,吗啡戒断大鼠脊髓和脑干中NR_(1A)和NR_(2A)表达显著高于依赖组,经NMDA受体拮抗剂MK801 (0.125 mg/kg,i.p.)、M受体拮抗剂东莨菪碱(0.5 mg/kg,i.p.)、M_(1)受体拮抗剂呱伦西平(10 mg/kg,i.p.)和NOS抑制剂L-NAME(10 mg/kg,i.p.)处理后,脊髓和脑干中NR_(1A)和NR_(2A)基因表达都较戒断组明显减少。在纳洛酮激发前24h鞘内注射NR_(1A)和M_(2)受体的反义寡脱氧核苷酸(4 #mu#g/只),戒断症状评分值及脊髓和脑干的NR_(1A) mRNA的表达均较对照组明显减少。吗啡依赖大鼠在纳洛酮注射前24h鞘内注射M_(2)受体反义寡脱氧核苷酸(4#mu#g/只),可以明显减少PAG内透析液中谷氨酸含量。上述结果显示:NMDA受体的基因表达和谷氨酸释放参与吗啡戒断过程,而这种表达受到M受体的调节。

关键词： 吗啡依赖; 成断反应; NMDA受体; 毒蕈碱乙酰胆碱受体; 一氧化氮合酶

Muscarinic receptors modulate the mRNA expression of NMDA receptors in brainstem and the release of glutamate in periaqueductal grey during morphine withdrawal in rats

Liu Huifen, Zhou Wenhua, Xie Xiaohu, Cao Junli, Gu Jun, Yang Guodong

Ningbo Instittue of Microcirculation & Henbane, Ningbo Addiction Research and Treatment Center.Ningbo 315010,Zhejiang

Abstract

The results suggest that the expression of NMDA receptors and the release of glutmate in brainstem are involved in the processes of morphine withdrawal and that the NMDA receptor expression is possibly regulated by the muscarinic receptors during morphine whthdrawal.

Key words: morphine dependence;withdrawal symptom;NMDA receptors;nitric oxide synthase;muscannic receptors

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引用本文：

刘惠芬, 周文华, 谢小虎, 曹君利, 顾钧, 杨国栋. M受体对吗啡戒断大鼠脊髓和脑干NMDA受体基因表达及中脑导水管周围灰质中谷氨酸释放的调节[J]. 生理学报 2004; 56 (1): .

Liu Huifen, Zhou Wenhua, Xie Xiaohu, Cao Junli, Gu Jun, Yang Guodong. Muscarinic receptors modulate the mRNA expression of NMDA receptors in brainstem and the release of glutamate in periaqueductal grey during morphine withdrawal in rats. Acta Physiol Sin 2004; 56 (1): (in Chinese with English abstract).