腹侧被盖区微注射MK-801对大鼠吗啡戒断症状的影响  

Microinjection of MK-801 into ventral tegmental area reduces naloxone-precipitated morphine withdrawal in rats

作　　者：王惠玲[1] 赵晏[1] 向晓辉[1] 王会生[1] 

机构地区：[1]环境与疾病相关基因教育部重点实验室

出　　处：《第四军医大学学报》2004年第16期1448-1451,共4页Journal of the Fourth Military Medical University

基　　金：陕西省自然科学基金资助项目 (2 0 0 2C1 2 2 )

摘　　要：目的 :研究中脑—边缘多巴胺回路腹侧被盖区(VTA)内源性谷氨酸信号转导在吗啡戒断形成中的作用 .方法 :给VTA微注射不同剂量谷氨酸NMDA受体拮抗剂(+)MK 80 1 ,用行为学方法观察对吗啡戒断大鼠戒断症状的影响 .递增量吗啡ip 7d建立依赖模型 ,末次给药 1 .5hip盐酸纳洛酮 (2mg/kg)诱发戒断症状 ,以Gellert HoltzmanScore和湿狗样颤为评价戒断症状程度的指标 ,进行统计学分析 .结果 :(+)MK 80 1 (2 ,5 ,1 0 g/L)微注射于VTA可明显减弱吗啡戒断大鼠湿狗样颤的发生次数 ,且能显著降低吗啡戒断鼠的Gellert HoltzmanScore.结论 :VTA内源性谷氨酸受体及其与中脑—边缘多巴胺能信号转导相互作用 ,参与吗啡戒断的形成 。AIM: To study whether the blockade of glutamate NMDA receptors in the ventral tegmental area (VTA) modulates the morphine withdrawal in rats. METHODS: The effects of (+) MK 801, microinjected unilaterally into the VTA 30 min before naloxone (2 mg/kg, ip) administration, on the morphine withdrawal were assessed. Morphine dependence developed with increasing morphine injection (ip) and morphine withdrawal was induced by injection (ip) of naloxone (2 mg/kg). Wet dog shakes and Gellert Holtzman score were used as the indexes to evaluate the intensity of morphine withdrawal. RESULTS: Unilateral microinjection of MK 801 into the VTA significantly reduced the Gellert Holtzman score and the incidence of wet dog shakes in morphine withdrawal rats. CONCLUSION: MK 801 (2, 5, 10 g/L) unilaterally administered into the VTA significantly reduces the intensity of morphine withdrawal syndrome in dependent rats. These data support that glutamatergic transmission in the VTA and its interactions with dopaminergic neurons in the mesolimbic system play some important roles in opiate withdrawal syndrome. Our findings also suggest a potential use of NMDA antagonists in the therapeutic treatment of opiate abuse.

关 键 词：腹侧被盖区 吗啡依赖 物质禁断综合征受体 N-甲基-D-天冬氨酸 MK-801 大鼠 

分 类 号：R971.92[医药卫生—药品]