Chrobak James J, Hinman James R, Sabolek Helen R
Department of Psychology, University of Connecticut, Storrs, Connecticut 06269, USA.
J Neurosci. 2008 Apr 23;28(17):4512-20. doi: 10.1523/JNEUROSCI.0742-07.2008.
Memories of events that occur often are sensitive to interference from memories of similar events. Proactive interference plays an important and often unexamined role in memory testing for spatially and temporally unique events ("episodes"). Ketamine (NMDA receptor antagonist) treatment in humans and other mammals induces a constellation of cognitive deficits, including impairments in working and episodic memory. We examined the effects of the ketamine (2.5-100 mg/kg) on the acquisition, retrieval, and retention of memory in a delayed-match-to-place radial water maze task that can be used to assess proactive interference. Ketamine (2.5-25 mg/kg, i.p.) given 20 min before the sample trial, impaired encoding. The first errors made during the test trial were predominantly to arms located spatially adjacent to the goal arm, suggesting an established albeit weakened representation. Ketamine (25-100 mg/kg) given immediately after the sample trial had no effect on retention. Ketamine given before the test trial impaired retrieval. First errors under the influence of ketamine were predominantly to the goal location of the previous session. Thus, ketamine treatment promoted proactive interference. These memory deficits were not state dependent, because ketamine treatment at both encoding and retrieval only increased the number of errors during the test session. These data demonstrate the competing influence of distinct memory representations during the performance of a memory task in the rat. Furthermore, they demonstrate the subtle disruptive effects of the NMDA antagonist ketamine on both encoding and retrieval. Specifically, ketamine treatment disrupted retrieval by promoting proactive interference from previous episodic representations.
经常发生的事件的记忆对来自相似事件记忆的干扰很敏感。在对空间和时间上独特的事件(“情节”)进行记忆测试时,前摄干扰起着重要且常常未被审视的作用。在人类和其他哺乳动物中,氯胺酮(NMDA受体拮抗剂)治疗会引发一系列认知缺陷,包括工作记忆和情节记忆受损。我们研究了氯胺酮(2.5 - 100毫克/千克)对延迟匹配位置放射状水迷宫任务中记忆的获取、检索和保持的影响,该任务可用于评估前摄干扰。在样本试验前20分钟给予氯胺酮(2.5 - 25毫克/千克,腹腔注射)会损害编码。测试试验期间首次出现的错误主要出现在与目标臂空间相邻的臂上,这表明存在一种既定但已减弱的表征。在样本试验后立即给予氯胺酮(25 - 100毫克/千克)对保持没有影响。在测试试验前给予氯胺酮会损害检索。在氯胺酮影响下的首次错误主要出现在上一阶段的目标位置。因此,氯胺酮治疗促进了前摄干扰。这些记忆缺陷并非状态依赖性的,因为在编码和检索时给予氯胺酮只会增加测试阶段的错误数量。这些数据证明了在大鼠执行记忆任务期间不同记忆表征的竞争影响。此外,它们还证明了NMDA拮抗剂氯胺酮对编码和检索的微妙破坏作用。具体而言,氯胺酮治疗通过促进来自先前情节表征的前摄干扰来破坏检索。