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NMDA 拮抗剂地卓西平(MK-801)的作用受啮齿动物嗅觉跨度工作记忆任务中分心刺激数量的调节。

Effects of NMDA antagonist dizocilpine (MK-801) are modulated by the number of distractor stimuli in the rodent odor span task of working memory.

机构信息

Department of Psychology, University of North Carolina at Wilmington, United States.

Department of Psychology, University of North Carolina at Wilmington, United States.

出版信息

Neurobiol Learn Mem. 2019 May;161:51-56. doi: 10.1016/j.nlm.2019.03.004. Epub 2019 Mar 9.

Abstract

The rodent odor span task (OST) uses an incrementing non-matching to sample procedure in which a series of odors is presented and selection of the session-novel odor is reinforced. An OST is frequently used to test the effects of neurobiological variables on memory capacity as the number of odors to remember increases during the course of the session. In this regard, one important finding has been that NMDA receptor antagonists selectively impair OST performance at doses that spare accuracy on control tasks. However, in many versions of the odor span task the number of stimuli to remember is confounded with the number of distractor odors presented to the rat on each trial. The present study compared the effects of the NMDA antagonist dizocilpine when the number of choices was held constant at two (one novel odor-S+ and one previously presented distractor odor-S-) and when the number of choice stimuli was permitted to increase up to 10 (one S+ and 9 S-). Dizocilpine impaired OST accuracy at doses that had no effect on a reference memory control task in both 2-choice and 10-choice conditions; however, the dose-response function was shifted to the left in the 10-choice tests. The impairments produced by dizocilpine were exacerbated as the memory load increased in both 2- and 10-choice conditions. These findings support the hypothesis that NMDA antagonism reduces the number of stimuli that rats can remember accurately, but the interaction between the effective DZP dose and the number of distractors shows that drug effects on OST performances may involve attentional factors in addition to memory capacity. The findings also demonstrate that variations in number of OST distractors can be used to alter sensitivity of the task.

摘要

啮齿动物气味跨度任务 (OST) 使用递增的非匹配采样程序,其中一系列气味被呈现,并且选择会话新颖气味得到加强。OST 常用于测试神经生物学变量对记忆容量的影响,因为在会话过程中要记住的气味数量会增加。在这方面,一个重要的发现是,NMDA 受体拮抗剂在剂量上选择性地损害 OST 性能,而这些剂量不会影响对照任务的准确性。然而,在许多版本的气味跨度任务中,要记住的刺激数量与大鼠在每次试验中呈现的干扰气味数量混淆。本研究比较了 NMDA 拮抗剂地卓西平在选择数量保持在两个(一个新颖气味-S+和一个先前呈现的干扰气味-S-)和选择刺激数量允许增加到 10 个(一个 S+和 9 个 S-)时的影响。地卓西平在 2 选择和 10 选择条件下,在对参考记忆控制任务没有影响的剂量下损害 OST 准确性;然而,剂量-反应函数在 10 选择测试中向左移动。在 2 选择和 10 选择条件下,随着记忆负荷的增加,地卓西平产生的损伤加剧。这些发现支持 NMDA 拮抗作用降低大鼠可以准确记住的刺激数量的假设,但地卓西平的有效剂量与干扰气味数量之间的相互作用表明,药物对 OST 性能的影响可能除了记忆容量之外还涉及注意力因素。这些发现还表明,OST 干扰气味数量的变化可用于改变任务的敏感性。

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