Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat
Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat
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DOI：
10.1016/s0306-4522(96)00202-3
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发表时间：
1996-10-01
期刊：
影响因子：
3.3
通讯作者：
Brioni, JD
中科院分区：
文献类型：
--
作者：
Gasbarri, A;Sulli, A;Brioni, JD
海马结构长期以来被认为在学习和记忆中发挥作用。本实验室以前的研究检查了大鼠中脑投射到海马结构的组织。为了评价逆行选择性损毁中脑多巴胺能神经元对学习记忆的影响，在双侧海马结构的背侧和腹侧下托及邻近CAI区注射6-羟基多巴胺后，对年轻成年Sprague-Dawley大鼠进行经典抑制性回避训练，使用多重试验（训练至标准）和标准Morris水迷宫任务（线索和空间版本）的抑制性回避。关于抑制性回避，在训练后1天、3天和10天检查保留。关于Morris水迷宫任务，6-羟基多巴胺损伤和假手术大鼠在四天的每一天接受四次训练试验。在训练期后，在60-s探测试验（自由游泳试验）期间测试大鼠，其中将平台从迷宫中移除。酪氨酸羟化酶免疫组化证实，与假手术大鼠相比，6-羟基多巴胺损伤大鼠中脑多巴胺能神经元的损失。虽然6-羟基多巴胺损毁组大鼠在Morris水迷宫的抑制性回避和线索化任务中与假手术组大鼠无明显区别，但在Morris水迷宫的空间任务中，损毁组大鼠与对照组相比，在潜伏期上表现出显著差异（P < 0.05），象限时间（P < 0.01）和平台交叉次数这些结果表明，大鼠获得空间，在Morris水迷宫中定位导航的学习和记忆也可能依赖于海马中多巴胺能连接的完整性。版权所有（C）1996 IBRO。出版社：Elsevier Science Ltd
The hippocampal formation has long been thought to play a role in learning and memory. Previous studies from our laboratory examined the organization of mesencephalic projections to the hippocampal formation in the rat. In order to evaluate the effects on learning and memory of retrograde selective lesions of mesencephalic dopaminergic neurons, following bilateral injection of 6-hydroxydopamine in the dorsal and ventral subiculum and adjacent CAI field of the hippocampal formation, young adult Sprague-Dawley rats were trained in classical inhibitory avoidance, inhibitory avoidance using a multiple trial (training to criterion) and the standard Morris water maze task (cued and spatial versions). With regard to inhibitory avoidance, retention was examined one, three and 10 days after training. Concerning the Morris water maze task, 6-hydroxydopamine-lesioned and sham-operated rats received four training trials on each of four days. After training sessions, the rats were tested during a 60-s probe trial (free-swim trial) in which the platform was removed from the maze. The loss of mesencephalic dopaminergic neurons in the 6-hydroxydopamine-lesioned rats, compared to sham-operated rats, was verified by tyrosine hydroxylase immunohistochemistry. Although the 6-hydroxydopamine-lesioned rats were indistinguishable from sham-operated rats in performing the inhibitory avoidance and the cued version of the Morris water maze task, in the spatial version of the Morris water maze, lesioned rats, compared to controls, exhibited significant differences in the latency (P < 0.05), quadrant time (P < 0.01) and number of platform crossings (P < 0.05).These results suggest that the rat's ability to acquire spatial,learning and memory for place navigation in the Morris water maze is likely to be dependent also on the integrity of mesohippocampal dopaminergic connections. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.