Yu Mei, Zhang Yuan, Chen Xiaoyu, Zhang Tao
a College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University , Tianjin , PR China.
Stress. 2016;19(1):104-13. doi: 10.3109/10253890.2015.1108302. Epub 2015 Nov 20.
The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.
本研究的目的是检验金刚烷胺（AMA）作为一种低亲和力非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，是否能够改善大鼠慢性应激所致的认知缺陷。雄性Wistar大鼠被分为四组：对照组、对照+AMA组、应激组和应激+AMA组。慢性应激模型将慢性不可预测应激（CUS）与单独饲养相结合。动物接受持续21天的CUS处理。从CUS第4天至第23天，AMA（25mg/kg）经口给药20天。在模型建立期间测量体重和蔗糖消耗量。使用莫里斯水迷宫（MWM）试验评估空间记忆。MWM试验后，在海马CA1区记录长时程增强（LTP）和去增强作用。通过蛋白质印迹分析测量NR2B和突触后致密蛋白95（PSD-95）蛋白。AMA增加了应激大鼠的体重和蔗糖消耗量。与对照组相比，应激大鼠的空间记忆和逆向学习受损，而AMA显著减轻了认知障碍。AMA还减轻了慢性应激诱导的海马突触可塑性损伤，其中应激大鼠的LTP和去增强作用均受到显著抑制。此外，AMA增强了应激大鼠海马NR2B和PSD-95的表达。数据表明，AMA可能是治疗类似抑郁症状及相关认知障碍的有效药物。
