摘要
目的探讨慢性吗啡依赖及戒断对大鼠伏隔核(NAc)、尾壳核(CPu)及海马(Hip)中NSF附着蛋白(SNAPs)表达的影响。方法成年♂Wistar大鼠,随机分为对照组、吗啡组和戒断不同时间组,吗啡组大鼠背部皮下注射吗啡8d,每日3次,剂量递增,对照组大鼠注射等体积生理盐水。吗啡组末次注射吗啡4h后处死,断头取脑。自然戒断组分别在戒断不同时间处死动物。各组均设平行对照。利用RT-PCR和Western blot技术分别检测各脑区SNAPs的mRNA和蛋白表达水平。结果与对照组相比,慢性吗啡依赖大鼠CPu内γ-SNAP的mRNA和蛋白表达水平均上调25%左右(P<0.01),NAc及Hip脑区则无明显变化,自然戒断d2、d3、d7组亦未观察到γ-SNAP明显的表达改变。α-SNAP和β-SNAP在吗啡依赖和自然戒断状态下3个被检脑区(NAc、CPu、Hip)均未检测到明显的表达变化。结论慢性吗啡依赖可增加CPu内γ-SNAP的表达,对α-SNAP和β-SNAP的表达没有影响,提示SNAPs 3种亚型在慢性吗啡依赖过程中行使不同的功能,可能与特定神经递质的分泌有关。慢性吗啡依赖及戒断引起的突触前神经递质释放改变可能不是由α-SNAP和β-SNAP表达量变化介导的,其具体机制可能与其内在活性变化或蛋白在细胞内的转位有关。
Aim To investigate the effects of chronic morphine treatment and withdrawal on the level of SNAPs in different brain regions of rats, including nu- cleus accumbens （ NAc）, caudate putamen （CPu） and hippocampus （Hip）. Methods Adult male Wistar rats were randomly assigned into control, morphine and spontaneous withdrawal group. The morphine dependent rat model was established by subcutaneous morphine injection with increasing doses for 8 d, three times a day （ 8：00,12：00, and 18：00 ）. The control group was injected with the same volume of normal saline. Rats in morphine group were killed 4 h after the last injection, and rats in withdrawl group were killed at indicated time. Control groups were paralleled with all treatment groups. The brains were removed and the NAc, CPu and Hip were separated. The expression of SNAPs mR- NA and protein were determined by RT-PCR and Westem blot. Results The expression of γ-SNAP in CPu of morphine dependent rats was up-regulated by about 25% （P 〈0. 01） ,and no alteration of γ-SNAP in NAc or Hip was detected in morphine dependent and with- drawal groups, a-SNAP and 13-SNAP were not changed in NAc, CPu and Hip of rats in morphine dependent and withdrawal groups. Conclusions Morphine de- pendence could lead to up-regulation of γ-SNAP in CPu,but it had no effects on the expression of α-SNAP and β-SNAP in NAc, CPu and Hip, which suggested that 3 isoforms of SNAPs function differently in mor- phine dependence and might be related with the secre- tion of specific neurotransmitter. The regulation of pres-ynaptic neurotransmitter release in morphine depend- ence and withdrawal was not mediated by the level of α-SNAP and β-SNAP, and the intracellular transloca- tion and intrinsic activity alteration of α-SNAP and β- SNAP might contribute to the molecular mechanisms underlying morphine dependence and withdrawal.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2008年第5期616-621,共6页
Chinese Pharmacological Bulletin
基金
国家重点基础研究发展计划(973计划)项目资助课题(No2003CB515400)
关键词
吗啡依赖
戒断综合征
NSF附着蛋白
伏隔核
尾壳核
海马
morphine dependence
withdrawal syn-drome
SNAP
necleus accumbens
caudate putamen
hippocampus
