Subchronic memantine administration on spatial learning, exploratory activity, and nest-building in an APP/PS1 mouse model of Alzheimer's disease
Subchronic memantine administration on spatial learning, exploratory activity, and nest-building in an APP/PS1 mouse model of Alzheimer's disease
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DOI：
10.1016/j.neuropharm.2011.01.035
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发表时间：
2011-05-01
影响因子：
4.7
通讯作者：
Rivest, Serge
中科院分区：
文献类型：
--
作者：
Filali, Mohammed;Lalonde, Robert;Rivest, Serge
谷氨酸神经毒性已被提出参与阿尔茨海默病的发病机制，临床数据支持成功的治疗与NMDA受体拮抗剂美金刚。在本研究中，评估了亚慢性美金刚胺给药对APP/PS1突变小鼠的空间和非空间学习以及探索活动和筑巢的影响。美金刚（10 mg/kg，i. p.）在左-右辨别的逆转期，尽管与Morris水迷宫和被动回避学习的生理盐水相当，但优于安慰剂。该药物对高架十字迷宫探索和筑巢中的非学习行为没有影响。这些结果支持NMDA受体拮抗剂对淀粉样病变突变小鼠行为灵活性的特异性作用。(C)2011爱思唯尔有限公司保留所有权利。
Glutamate neurotoxicity has been proposed to be involved in Alzheimer pathogenesis, with clinical data supporting succesful treatment with the NMDA receptor antagonist memantine. In the present study, the effects of subchronic memantine administration were assessed on spatial and non-spatial learning as well as exploratory activity and nest-building in APP/PS1 mutant mice. Memantine (10 mg/kg, i.p.) was better than placebo during the reversal phase of left-right discrimination, though equivalent to saline for Morris water maze and passive avoidance learning. The drug had no effect on non-learned behaviors in elevated plus-maze exploration and nest-building. These results support a specific action of the NMDA receptor antagonist on behavioral flexibility in mutant mice with amyloid pathology. (C) 2011 Elsevier Ltd. All rights reserved.