腹侧被盖区微注射MK.docVIP

腹侧被盖区微注射MK 【关键词】 吗啡依赖 　　【Abstract】 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 (+) MK801, 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 GellertHoltzman score were used as the indexes to evaluate the intensity of morphine withdrawal. RESULTS: Unilateral microinjection of MK801 into the VTA significantly reduced the GellertHoltzman score and the incidence of wet dog shakes in morphine withdrawal rats. CONCLUSION: MK801 (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. 　　【Keywords】 MK801; Morphine deperdence; substance withdrawal syndrome; receptors, NmethylDaspartate; Rats; ventral tegmental area 　　【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（+）MK801，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 7 d建立依赖模型，末次给药1.5 h ip盐酸纳洛酮（2 mg/kg）诱发戒断症状，以GellertHoltzman Score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： （+）MK801（2， 5， 10 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GellertHoltzman Score. 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，提示谷氨酸受体拮抗剂可用于吗啡戒断的治疗. 　　【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；MK801；大鼠 　　0引言 　　阿片依赖是一种细胞适应性反应，许多脑区参与，中脑―边缘多巴胺回路系其中之一. 研究表明吗啡戒断大鼠腹侧被盖区（VTA）多巴胺神经元直径、数目减小［1］，放电频率及多巴胺释放量降低［2，3］，可见VTA多巴胺神经元功能下调. VTA多巴胺能神经元既接受自身受体D2的调节，又接受谷氨酸能投射. 激动VTA谷氨酸受体可增加伏隔核多巴胺释放和大鼠运动行为［4］，重复给予吗