Araujo J A, Chan A D F, Winka L L, Seymour P A, Milgram N W
Department of Pharmacology, University of Toronto, 1 King's College Circle, M5S 1A8, Toronto, ON, Canada.
Psychopharmacology (Berl). 2004 Aug;175(1):92-8. doi: 10.1007/s00213-004-1777-y. Epub 2004 Mar 17.
The cholinergic system is linked extensively to memory, but its exact role remains controversial. In particular, scopolamine-induced impairment in rodents is not task specific, which may be due to difficulty in developing rodent protocols to assess deficits in recent memory, in which the remembered event is brief and distinct, and/or to non-specific behavioral impairment.
The present study sought to determine whether scopolamine-induced deficits in recent memory, using a working memory task, could be dose-specifically dissociated from deficits in associative memory in dogs.
A Latin-square design was used to determine the effect of scopolamine (5, 10 and 15 microg/kg; SC) on a variable delayed-non-matching-to-position (DNMP) task, which assesses visuospatial working memory. Subsequently, the minimal effective dose (15 microg/kg; SC) was administered prior to testing on a landmark discrimination task, which provides a measure of allocentric spatial ability, a black-white discrimination task, an oddity discrimination task and tests of exploratory behavior. We also investigated the effects of a 30 microg/kg dose (SC) on tests of oddity discrimination and behavioral activity.
A 15 microg/kg dose produced significant impairment on the DNMP task, but did not affect performance of any discrimination task and did not alter behavior on tests of open field or curiosity. A 30 microg/kg dose caused disruption on discrimination performance and on open field measures.
Working memory performance is most sensitive to scopolamine-induced impairment and can be dissociated from scopolamine-induced deficits in discrimination performance and non-cognitive behaviors. The present results indicate that scopolamine-induced impairments of working memory in the dog can serve as a model of age-related cholinergic dysfunction.
胆碱能系统与记忆广泛相关,但其确切作用仍存在争议。特别是,东莨菪碱诱导的啮齿动物记忆损伤并非任务特异性的,这可能是由于难以制定啮齿动物实验方案来评估近期记忆缺陷,其中记忆事件短暂且独特,和/或由于非特异性行为损伤。
本研究旨在确定使用工作记忆任务时,东莨菪碱诱导的近期记忆缺陷是否能与犬类联想记忆缺陷呈现剂量特异性分离。
采用拉丁方设计来确定东莨菪碱(5、10和15微克/千克;皮下注射)对可变延迟位置不匹配(DNMP)任务的影响,该任务评估视觉空间工作记忆。随后,在进行地标辨别任务(可测量以自我为中心的空间能力)、黑白辨别任务、奇异性辨别任务和探索行为测试之前,给予最小有效剂量(15微克/千克;皮下注射)。我们还研究了30微克/千克剂量(皮下注射)对奇异性辨别测试和行为活动的影响。
15微克/千克剂量对DNMP任务产生显著损伤,但不影响任何辨别任务的表现,也不改变旷场或好奇心测试中的行为。30微克/千克剂量导致辨别性能和旷场测量结果受到干扰。
工作记忆表现对东莨菪碱诱导的损伤最为敏感,并且可以与东莨菪碱诱导的辨别性能和非认知行为缺陷相分离。目前的结果表明,东莨菪碱诱导的犬类工作记忆损伤可作为与年龄相关的胆碱能功能障碍的模型。