Winocur Gordon, Wojtowicz J Martin, Tannock Ian F
Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, ON M6A 2E1, Canada; Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, M5T1X8, Canada; Department of Psychology, Trent University, 1600 West Bank Dr, Peterborough, ON K9J 7B8, Canada.
Department of Physiology, University of Toronto, Toronto, ON M5S 1E8, Canada.
Behav Brain Res. 2015 Mar 15;281:239-44. doi: 10.1016/j.bbr.2014.12.028. Epub 2014 Dec 18.
Drugs used to treat cancer have neurotoxic effects that often produce memory loss and related cognitive deficits. In a test of the hypothesis that chemotherapy-induced cognitive impairment is related to a loss of inhibitory control, rats injected with a combination of methotrexate+5-fluouracil or equal volumes of saline, were administered a retroactive interference task in which memory for a learned discrimination problem was tested under conditions of high- and low-interference. The drugs had no effect on original learning or on re-learning the discrimination response when there was little interference, but the chemotherapy group was severely impaired in the hippocampus-sensitive, high-interference memory test. The impaired performance correlated significantly with reduced neurogenesis in the hippocampus. The failure to suppress interfering influences is consistent with a breakdown in pattern separation, a process that distinguishes and separates overlapping neural representations of experiences that have a high degree of similarity.
用于治疗癌症的药物具有神经毒性作用，常常会导致记忆丧失和相关的认知缺陷。在一项关于化疗诱导的认知障碍与抑制控制丧失有关的假设测试中，给注射了甲氨蝶呤+5-氟尿嘧啶组合或等量生理盐水的大鼠进行了一项逆向干扰任务，即在高干扰和低干扰条件下测试对已学会的辨别问题的记忆。当干扰很小时，这些药物对原始学习或重新学习辨别反应没有影响，但化疗组在海马体敏感的高干扰记忆测试中严重受损。表现受损与海马体中神经发生减少显著相关。无法抑制干扰影响与模式分离功能的崩溃一致，模式分离是一个区分和分离具有高度相似性的重叠神经表征的过程。
