金刚烷胺诱发小鼠行为学变化和前脑内FosB/δFosB蛋白的表达(英文)  

Amantadine-induced ethological changes and the over-expression FosB/δFosB in mice forebrain

作　　者：马传响[1] 张静[1] 刘芳[2] 宋亮[2] 王德广[1] 陈幽婷[1] 

机构地区：[1]徐州医学院解剖学教研室,徐州221004 [2]徐州医学院神经生物学教研室,徐州221004

出　　处：《神经解剖学杂志》2010年第6期587-593,共7页Chinese Journal of Neuroanatomy

基　　金：徐州市科技计划项目(XM07C057)~~

摘　　要：目的:探讨临床使用金刚烷胺(amantadine)治疗流行感冒或帕金森病(PD)时导致患者出现精神症状副作用的中枢机制,给予小鼠不同剂量金刚烷胺,评价其行为学的改变,同时检测小鼠脑内FosB/δFosB蛋白的表达。方法:雄性昆明小鼠,随机分为生理盐水组、金刚烷胺组(20mg/kg、40mg/kg、60mg/kg),分别用自主活动观察、Sams-Dodd的刻板行为评分标准、一次性被动回避反应(OPAR)等模式对模型小鼠的行为改变进行检测,同时用免疫组织化学法检测各组小鼠脑内FosB/δFosB蛋白的表达。结果:(1)高浓度的金刚烷胺(60mg/kg)作用于小鼠,小鼠的自主活动较对照组有不同程度的提高,并且出现明显的刻板行为及社会行为的降低。中(40mg/kg)、低(20mg/kg)浓度的金刚烷胺作用于小鼠,小鼠的自主活动较对照组无明显差异;(2)金刚烷胺以剂量相关性方式改变FosB/δFosB蛋白的表达,其表达区域主要集中在前额皮质、扣带皮质、梨状皮质、齿状回、隔区、伏隔核、杏仁核和嗅结节等脑区。结论:(1)大剂量的金刚烷胺能够引起小鼠的行为变化。(2)FosB/δFosB阳性细胞高表达的区域主要集中在前脑内与情绪活动和内脏活动功能密切相关的脑区,这些区域脑神经元的功能变化可能是临床使用金刚烷胺导致患者出现精神症状副作用的原因之一。Objective：To evaluate the underlying mechanisms of the sideeffets induced by such as psychiatric symptoms amantadine in clinical treatment of influenza or Parkinson’s disease（PD）,the effect of amantadine of different doses on the ethology and FosB/δFosB expression in forebrain of mice was investigated.Methods：Male Kunming mice were equally randomized into normal saline group and amantadine（20 mg/kg,40 mg/kg and 60 mg/kg） groups,and their ethological changes were determined by spontaneous activity observation,Sams-Dodd stereotyped behavior scores and once passive avoidance response（OPAR） respectively.Meanwhile,immunohistochemical method was used to detect and evaluate the forebrain FosB/δFosB expression in mice in all groups.Results：（1） When treated with amantadine in a high dose（60 mg/kg）,the mice showed more active spontaneous activities,evident stereotyped behaviors and social isolation;whereas the groups treated with medium and low-dose（40 mg/kg and 20 mg/kg） amantadine showed no differences compared with the control group.（2） Amantadine could alter the expression of FosB/δFosB in a dose-dependentmanner,with the expression mostly located in prefrontal cortex,cingulate cortex,pyriform cortex,dentate gyrus,septal area,accumbens nucleus,amygdala and olfactory tubercles.Conclusion：（1） Large dose of amantadine could induce ethological changes in Kunming mice;（2） The FosB/δFosB positive cells were mainly located in the areas closely related to the psychoactivity and visceral motility in forebrain.The functional changes of the neurons in these areas may be one of the reasons for the amantadine-induced psychiatric symptoms in clinical application.

关 键 词：金刚烷胺 FosB/δFosB 精神症状 小鼠 

分 类 号：R965[医药卫生—药理学]