Time gradient for post-test vulnerability to scopolamine-induced amnesia following the initial acquisition session of a spatial reference memory task in mice

Abdoulaye Toumane , Thomas P. Durkin
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引用次数: 19

Abstract

The time course for vulnerability to the amnestic effects of the cholinergic antagonist, scopolamine, during the postacquisition period has been investigated. We have examined the effects of post-test injections of scopolamine (1 mg/kg ip) given at different times from 30 s for up to 6 h following the end of the first acquisition session of a concurrent spatial discrimination (reference memory) protocol in an 8-arm radial maze on subsequent long-term (24 h) retention performance in C57BL/6 mice. Results show that the immediate (30 s) post-test injection of scopolamine—HCl on Day 1 produces marked perturbation (amnesia) of long-term retention as attested to by significant deficits in various indices of spatial discrimination performance gain on Day 2 as compared to control subjects injected either with scopolamine—MBr or saline. The severity of this scopolamine-induced amnesia declines only slightly as a function of the treatment period 30 s—3 h post-test. However, no evidence for amnesia is observed if scopolamine—HCl injections are delayed for 6 h postsession. This important latter observation attests to the absence of any significant proactive effects of scopolamine on the ability of mice to perform the retention test via possible long-term effects on attention, motivation, or locomotor performance. These results thus constitute evidence for the existence of a limited (30 s–3 h) time gradient for vulnerability of the early memory trace to disruption by scopolamine. The present results are dis cussed in relation to our previous direct neurochemical observations describing the differential time courses of intervention of the ascending septohippocampal and nBM—cortical cholinergic pathways in the postlearning period. In particular, the presently observed time window concerning post-test vulnerability to scopolamine-induced amnesia corresponds more closely to the time course of the acute activation of the nBM—cortical cholinergic pathway, induced by testing with the same spatial memory protocol as used in the present study in mice.

空间参考记忆任务初始习得阶段后东莨菪碱诱发失忆症的时间梯度
在习得后时期,对胆碱能拮抗剂东莨菪碱的遗忘效应的易感性的时间过程进行了研究。我们研究了在8臂径向迷宫中同步空间辨别(参考记忆)方案的第一次获取阶段结束后,在30秒至6小时的不同时间注射东莨菪碱(1 mg/kg / ip)对C57BL/6小鼠随后的长期(24小时)记忆保留性能的影响。结果表明,与注射东莨菪碱-盐酸或生理盐水的对照组相比,在第1天立即(30秒)注射东莨菪碱-盐酸会产生明显的长期记忆紊乱(失忆),这可以通过在第2天的空间辨别性能增加的各项指标显着下降来证明。东莨菪碱引起的健忘症的严重程度随着治疗时间的延长仅略有下降。然而,如果在治疗后延迟注射盐酸东莨菪碱6小时,没有观察到健忘症的证据。这一重要的后一项观察结果证明,东莨菪碱通过对注意力、动机或运动表现可能产生的长期影响,对小鼠执行保留测试的能力没有任何显著的主动影响。因此,这些结果构成了存在有限(30 s-3 h)时间梯度的证据,表明早期记忆痕迹易受东莨菪碱破坏。目前的结果与我们之前的直接神经化学观察结果有关,这些观察结果描述了学习后阶段中隔海马上升通路和nbm -皮质胆碱能通路干预的不同时间过程。特别是,目前观察到的东莨菪碱诱发健忘症的测试后易感性的时间窗与nbm -皮质胆碱能通路的急性激活的时间过程更为接近,这种激活是通过使用与本研究中使用的小鼠相同的空间记忆方案进行测试引起的。
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