Laboratory of Endocrinology and Genomics, CHUQ Research Center and Department of Molecular Medicine, Laval University, 2705 Boulevard Laurier, Québec G1V 4G2, Canada.
Neuropharmacology. 2011 May;60(6):930-6. doi: 10.1016/j.neuropharm.2011.01.035. Epub 2011 Jan 31.
Glutamate neurotoxicity has been proposed to be involved in Alzheimer pathogenesis, with clinical data supporting successful 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.
谷氨酸神经毒性被认为与阿尔茨海默病的发病机制有关，临床数据支持使用 NMDA 受体拮抗剂美金刚进行成功治疗。在本研究中，评估了亚慢性美金刚给药对 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。在左右辨别任务的反转阶段，美金刚（10mg/kg，腹腔注射）优于安慰剂，但在 Morris 水迷宫和被动回避学习方面与生理盐水等效。该药物对高架十字迷宫探索和筑巢等非学习行为没有影响。这些结果支持 NMDA 受体拮抗剂在具有淀粉样蛋白病理的突变小鼠中对行为灵活性具有特异性作用。
