Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat
Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat
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DOI：
10.1016/j.bbr.2007.06.012
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发表时间：
2007-11-22
影响因子：
2.7
通讯作者：
Neill, J. C.
中科院分区：
文献类型：
--
作者：
Grayson, B.;Idris, N. F.;Neill, J. C.
新的物体识别(NOR)任务是一种用来检测大鼠非空间记忆中断和改善的范式。PCP(苯环利定)可用于建立大鼠精神分裂症症状的模型，特别是认知缺陷。这项研究的目的是调查典型和非典型抗精神病药物使用NOR任务改善亚慢性PCP引起的认知障碍的能力。雌性Wistar大鼠(195+/-12g)给予生理盐水(每日两次)或五氯苯酚(2 mg/kg，每日两次)，连续7天，然后停药7天。氟哌啶醇(0.075.0 5和0.0 5 mg/kg)、氯氮平(1和5 mg/kg)、利培酮(0.0 5、0.1和0.2 mg/kg)或赋形剂(VEH、生理盐水)。测试前30分钟。大鼠完成一次习得试验，然后是一次间隔为1分钟的试验间隔，然后是一次保留试验。在亚慢性药物治疗后，与熟悉的物体相比，大鼠花在探索新奇事物上的时间明显更多(p<；0.05)，这种效应在亚慢性五氯苯酚治疗的动物中被取消。氯氮平(1.0和5.0 mg/kg)和利培酮(0.2 mg/kg)可显著减轻五氯苯酚所致的损伤，但氟哌啶醇无明显作用，使得动物与熟悉的对象相比，再次花费更多的时间探索新事物(p<；0.05)。这些结果支持了我们早期的工作，即急性PCP导致雌性大鼠强烈的物体识别缺陷。氯氮平和利培酮有逆转亚慢性PCP所致缺陷的作用，但氟哌啶醇无此作用，提示该测验对精神分裂症认知障碍症状的改善有一定的有效性。(C)2007 Elsevier B.V.保留所有权利。
The novel object recognition (NOR) task is a paradigm employed to detect both disruption and improvement of non-spatial memory in rats. PCP (phencyclidine) may be used to model aspects of schizophrenia symptomology in rats, in particular cognitive deficits. The aim of this study was to investigate the ability of typical and atypical antipsychotics to improve a sub-chronic PCP-induced impairment in cognition using the NOR task. Female hooded-Lister rats (195 +/- 12 g) received either vehicle (0.9% saline twice daily) or PCP (2 mg/kg, twice daily) for 7 days followed by 7-days drug free. Haloperidol (0.05 and 0.075 mg/kg), clozapine (1 and 5 mg/kg), risperidone (0.05, 0.1 and 0.2 mg/kg) or vehicle (veh, saline) was administered i.p. 30 min prior to testing. Rats completed an acquisition trial followed by an inter-trial interval of I min, then a retention trial. Following sub-chronic vehicle treatment, rats spent significantly (p < 0.05) more time exploring the novel compared to the familiar object, an effect that was abolished in the sub-chronic PCP treated animals. Clozapine (1.0 and 5.0 mg/kg) and risperidone (0.2 mg/kg) but not haloperidol significantly attenuated the PCP-induced impairment such that animals again spent significantly more time exploring the novel compared with familiar object (p < 0.05). These results support our earlier work showing that acute PCP induces a robust object recognition deficit in female rats. Clozapine and risperidone but not haloperidol showed efficacy to reverse the deficit induced by sub-chronic PCP suggesting that this test may have some validity for assessing efficacy for improvement of cognitive deficit symptoms of schizophrenia. (C) 2007 Elsevier B.V. All rights reserved.