Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats
Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats
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DOI：
10.1016/j.bbr.2011.03.069
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发表时间：
2011-10-01
影响因子：
2.7
通讯作者：
Christoffersen, Gert R. J.
中科院分区：
文献类型：
--
作者：
Clausen, Bettina;Schachtman, Todd R.;Christoffersen, Gert R. J.
D1型受体拮抗已知会损害啮齿动物的记忆，但也会抑制对刺激的自发探索，以供记忆。低探索可能通过影响事件处理而导致记忆受损。为了探讨这种作用，大鼠分别通过影响或不影响自发探索的途径，即全身给药或初步给药，给大鼠注射D1受体拮抗剂SCH23390。对空间记忆任务和非空间记忆任务的记忆效应进行了测试，选择空间记忆任务和非空间记忆任务对记忆的影响进行了考察。系统管理减少了在跨迷宫和开阔场地测试中的空间探索，也减少了物体探索。空间(依赖于海马体)的短期记忆在交叉迷宫中受到抑制，非空间短期物体保持能力也受到损害。与这些全身性效应相反，将SCH23390注射到大脑皮层前部，既没有改变空间探索，也没有改变物体探索，但确实抑制了在跨迷宫和物体识别任务中的短期记忆。因此，SCH23390对空间和非空间记忆的抑制作用不是通过减少对要记忆的刺激的探索间接实现的，而是通过拮抗直接参与记忆形成的初步的D1-R功能来实现的。拮抗剂SCH23390和MPEP的协同作用表明，d1-R和mGlu5之间存在空间探索的协同调节。(C)2011爱思唯尔B.V.保留所有权利。
D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390, was administered to rats via routes that either did or did not affect spontaneous exploration: systemic or prelimbic administration, respectively. Effects were tested in spatial and non-spatial memory tasks selected for their requirements for self-initiated exploration of stimuli to be remembered in order to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non-spatial short-term object retention was also impaired. In contrast to these systemic effects, bilateral injections of SCH23390 into the prelimbic cortices altered neither spatial nor object exploration, but did inhibit short-term memory in both cross-maze and object recognition task. Therefore, the inhibiting effects of SCH23390 on both spatial and non-spatial memory were not mediated indirectly via reduced exploration of stimuli to be remembered, but through antagonism of a prelimbic D1-R function that is directly involved in memory formation. Finally, a cooperative regulation of spatial exploration between D1-R and mGlu5 was indicated by a synergistic effect of the antagonists SCH23390 and MPEP. (C) 2011 Elsevier B.V. All rights reserved.