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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 investigate the central mechanism of amantadine in the treatment of influenza or Parkinson’s disease (PD) in patients with psychiatric symptoms and side effects and to evaluate the behavioral changes of amantadine in mice at the same time. Expression of FosB / δFosB in mouse brain. Methods: Male Kunming mice were randomly divided into normal saline group, amantadine group (20mg / kg, 40mg / kg, 60mg / kg), and were evaluated by voluntary activity and Sams-Dodd’s score (OPAR) and other patterns of behavioral changes in model mice were detected at the same time by immunohistochemistry to detect the brain FosB / δ FosB protein expression in each group. RESULTS: (1) Amantadine (60mg / kg) was administered to mice at a high concentration. The autonomic activity of mice increased to some extent compared with that of the control group, and obvious stereotyped behavior and social behavior decreased. (40mg / kg), low (20mg / kg) concentration of amantadine in mice, spontaneous activity in mice compared with the control group no significant difference; (2) amantadine in a dose-dependent manner to change FosB /? FosB Protein expression, the expression of the region mainly in the prefrontal cortex, cingulate cortex, piriform cortex, dentate gyrus, septal, nucleus accumbens, amygdala and olfactory tubercle and other brain regions. Conclusion: (1) Large doses of amantadine can cause behavioral changes in mice. (2) The regions of high expression of FosB / δFosB positive cells mainly concentrated in the brain regions closely related to the emotional activities and visceral activities in the forebrain. The functional changes of the neurons in these regions may be caused by the clinical use of amantadine in the patients One of the causes of side effects of symptoms.