University of North Carolina Wilmington, Department of Psychology, 601 S. College Rd., Wilmington, NC 28403, USA.
Neurobiol Learn Mem. 2011 Jan;95(1):57-63. doi: 10.1016/j.nlm.2010.11.004. Epub 2010 Nov 11.
NMDA receptor antagonists interfere with learning and memory in some tasks, but not others. Some recent accounts have suggested that tasks placing demands on working memory are those most likely to be affected, and the present study tested this hypothesis. The purpose of the study was to adapt a recently developed procedure designed to test working memory capacity, the olfactory memory span task, for use in behavioral pharmacology and to then determine the effects of the NMDA receptor antagonist, dizocilpine (MK801) on performance in this task. Rats were trained in a non-match-to-sample procedure under conditions in which they had to remember an increasing number of olfactory stimuli as the session progressed. Simple olfactory discrimination trials were interspersed to provide a performance control. Effects of dizocilpine (.03, .10, .17, .3mg/kg) were determined after stable performances were obtained. Rats were able to sustain stable performances on both the span and simple discrimination tasks with average spans of about 10 items. Accuracy declined as the number of stimuli to remember increased, and dizocilpine impaired accuracy in a dose-dependent and memory-load dependent fashion. The finding that the effects of dizocilpine interacted with the number of stimuli to remember is generally consistent with hypotheses linking NMDA receptors and working memory processes.
NMDA 受体拮抗剂在某些任务中会干扰学习和记忆，但在其他任务中则不会。最近的一些研究表明，那些对工作记忆要求较高的任务最有可能受到影响，本研究检验了这一假设。本研究的目的是改编最近开发的一种用于测试工作记忆能力的程序，即嗅觉记忆跨度任务，以便在行为药理学中使用，然后确定 NMDA 受体拮抗剂地卓西平（MK801）对该任务表现的影响。大鼠在非匹配样本程序中接受训练，在该程序中，随着实验的进行，它们必须记住越来越多的嗅觉刺激。简单的嗅觉辨别试验穿插其中，为表现提供控制。在获得稳定的表现后，确定地卓西平（0.03、0.10、0.17、0.3mg/kg）的作用。大鼠能够在跨度和简单辨别任务上维持稳定的表现，平均跨度约为 10 个项目。随着要记住的刺激数量的增加，准确性下降，地卓西平以剂量和记忆负荷依赖的方式损害准确性。地卓西平的作用与要记住的刺激数量相互作用的发现，通常与将 NMDA 受体与工作记忆过程联系起来的假设一致。
