Repeated low dose of phencyclidine administration impairs spatial learning in mice:: Blockade by clozapine but not by haloperidol
Repeated low dose of phencyclidine administration impairs spatial learning in mice:: Blockade by clozapine but not by haloperidol
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DOI：
10.1016/j.euroneuro.2007.12.001
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发表时间：
2008-07-01
影响因子：
5.6
通讯作者：
Ogren, Sven Ove
中科院分区：
文献类型：
--
作者：
Beraki, Simret;Kuzmin, Alexander;Ogren, Sven Ove
在水迷宫实验中，研究了非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环利定（PCP）对海马功能依赖性空间学习记忆的影响。交配的成年C57 Bl/6 J小鼠每天接受（s.c.）注射生理盐水或五氯苯酚（0.25-4.0毫克/千克），持续12天。在最后5天期间，注射后进行水迷宫训练。在0.5-4.0 mg/kg剂量范围内，五氯苯酚重复处理会破坏空间学习和记忆。在2.0和4.0毫克/千克剂量的五氯苯酚下观察到严重的感觉运动障碍，因此无法进行进一步的游泳迷宫测试。0.5 mg/kg剂量的五氯苯酚（而不是1.0 mg/kg剂量的五氯苯酚）损害了空间学习和记忆，但没有任何明显的感觉运动缺陷。五氯苯酚浓度为1.0毫克/千克时，在游泳迷宫任务中的非空间学习能力受损，在转棒测试中的运动障碍。每天重复使用“非典型”抗精神病药物氯氮平（0.5 mg/kg i. p.）或“典型的”抗精神病药物氟哌啶醇（0.05mg/kg i. p.）对空间表现没有影响。0.5 mg/kg剂量PCP引起的空间障碍可通过与氯氮平（0.5 mg/kg）联合治疗而阻断，但与哈哌啶醇（0.05 mg/kg）不能阻断。结果提示，在两个剂量下，PCP的水迷宫空间学习障碍可能与NMDA受体阻断剂的不良行为效应无关。这一模型可能为分析精神分裂症陈述性记忆障碍的潜在机制以及典型和非典型抗精神病药物之间的机制差异提供了基础。(c)2007 Elsevier B. V.和ECNR保留所有权利。
The effect of phencyclidine (PCP), a non-competitive N-methyt-D-aspartate (NMDA) receptor antagonist, was examined in the water maze, a spatial learning and memory task dependent on hippocampal functions. Mate adult C57Bl/6J mice received daily (s.c.) injections of either saline or PCP (0.25-4.0 mg/kg) for 12 days. During the last 5 days, the injections were followed by water maze training. Repeated PCP treatments disrupted spatial learning and memory in the 0.5-4.0 mg/kg dose range. Severe sensorimotor disturbances, observed at the 2.0 and 4.0 mg/kg doses of PCP, precluded further swim maze testing. The 0.5 mg/kg but not the 1.0 mg/kg dose of PCP impaired spatial learning and memory without any apparent sensorimotor deficits. PCP, at 1.0 mg/kg, produced impairment in non-spatial learning in the swim maze task and motor disturbances in the rotarod test. Repeated daily treatment with either the "atypical" antipsychotic drug clozapine (0.5 mg/kg i.p.) or the "typical" antipsychotic drug haloperidol (0.05 mg/kg i.p.) failed to influence spatial performances. The spatial impairment caused by the 0.5 mg/kg dose of PCP was blocked by concomitant treatment with clozapine (0.5 mg/kg), but not with hatoperidol (0.05 mg/kg). The results suggest that it is possible, at tow doses of PCP, to dissociate the spatial Learning impairment in the water maze from the adverse behavioral effects of NMDA receptor blockade. This model may provide a basis for the analysis of the mechanisms underlying declarative memory disturbances in schizophrenia and the differences in mechanisms between typical and atypical antipsychotic drugs. (c) 2007 Elsevier B.V. and ECNR All rights reserved.