de Bruin Natasja, Pouzet Bruno
Johnson and Johnson/Pharmaceutical Research and Development (J&J PRD)/CNS Discovery Research Turnhoutseweg 30, B-2340 Beerse, Belgium.
Pharmacol Biochem Behav. 2006 Sep;85(1):253-60. doi: 10.1016/j.pbb.2006.08.007. Epub 2006 Sep 20.
Episodic memory has been found to be impaired in several neuropsychiatric disorders. The object recognition task (ORT), introduced by Ennaceur and Delacour [Ennaceur A., Delacour J. A new one-trial test for neurobiological studies of memory in rats: 1. Behavioral data. Behav Brain Res 1988; 31: 47-59.], is a method to measure a specific form of episodic memory in rats and mice. It is based on the spontaneous behavior of rodents and can be considered as a retention test completely free of reference memory components. Therefore, the ORT has been increasingly used as an experimental tool in assessing drug effects on memory and investigating the neural mechanisms underlying learning and memory. In the present study, the main goal was to evaluate the effects of galantamine in Swiss mice in the ORT on scopolamine-induced deficits and with different retention intervals. Mice had a good object recognition memory at the 15 min retention intertrial interval (ITI). Object discrimination was absent at the longer intervals (1 h, 4 h and 24 h). Galantamine (10 mg/kg, administered s.c., 30 min prior to acquisition) partially reversed effects of scopolamine (0.63 mg/kg, administered s.c., 30 min prior to acquisition) and normalized performance to control levels. A lower dose of galantamine (0.63 mg/kg) was also investigated when two different retention intervals (15 min and 1 h) were used. Galantamine (0.63 mg/kg) had no adverse effects. Solvent-treated mice in the 1 h ITI condition did not discriminate between the novel and the familiar object (discrimination index was equal to zero), while galantamine (0.63 mg/kg)-treated mice attained a good object recognition memory performance. In conclusion, galantamine was shown to possess memory-enhancing effects in two conditions that reduced object discrimination: scopolamine-induced deficits and when a longer retention interval was used.
人们发现,情景记忆在多种神经精神疾病中会受损。由恩纳瑟尔和德拉库尔[恩纳瑟尔A.,德拉库尔J.一种用于大鼠记忆神经生物学研究的新型单次试验测试:1.行为数据。行为脑科学研究1988年;31:47 - 59。]引入的物体识别任务(ORT),是一种测量大鼠和小鼠特定形式情景记忆的方法。它基于啮齿动物的自发行为,可被视为一种完全不含参照记忆成分的保持测试。因此,ORT越来越多地被用作评估药物对记忆的影响以及研究学习和记忆潜在神经机制的实验工具。在本研究中,主要目标是评估加兰他敏对瑞士小鼠在ORT中对抗东莨菪碱诱导的缺陷以及不同保持间隔的影响。小鼠在15分钟的保持试验间隔(ITI)时具有良好的物体识别记忆。在较长间隔(1小时、4小时和24小时)时不存在物体辨别。加兰他敏(10毫克/千克,皮下注射,在获取前30分钟给药)部分逆转了东莨菪碱(0.63毫克/千克,皮下注射,在获取前30分钟给药)的作用,并使表现恢复到对照水平。当使用两个不同的保持间隔(15分钟和1小时)时,还研究了较低剂量的加兰他敏(0.63毫克/千克)。加兰他敏(0.63毫克/千克)没有不良反应。在1小时ITI条件下接受溶剂处理的小鼠无法区分新物体和熟悉物体(辨别指数等于零),而接受加兰他敏(0.63毫克/千克)处理的小鼠获得了良好的物体识别记忆表现。总之,加兰他敏在两种降低物体辨别的情况下显示出记忆增强作用:东莨菪碱诱导的缺陷以及使用较长保持间隔时。