Grayson B, Idris N F, Neill J C
Bradford School of Pharmacy, University of Bradford, West Yorkshire, Bradford BD7 1DP, United Kingdom.
Behav Brain Res. 2007 Nov 22;184(1):31-8. doi: 10.1016/j.bbr.2007.06.012. Epub 2007 Jun 29.
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 5mg/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 1 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.
新颖物体识别（NOR）任务是一种用于检测大鼠非空间记忆障碍和改善情况的范式。苯环己哌啶（PCP）可用于模拟大鼠精神分裂症症状的某些方面，尤其是认知缺陷。本研究的目的是使用NOR任务研究典型和非典型抗精神病药物改善PCP亚慢性诱导的认知障碍的能力。雌性利斯特戴帽大鼠（195±12克）连续7天接受溶剂（0.9%生理盐水，每日两次）或PCP（2毫克/千克，每日两次），随后7天不使用药物。在测试前30分钟腹腔注射氟哌啶醇（0.05和0.075毫克/千克）、氯氮平（1和5毫克/千克）、利培酮（0.05、0.1和0.2毫克/千克）或溶剂（生理盐水）。大鼠完成一次获取试验，随后是1分钟的试验间隔，然后是一次保留试验。在亚慢性溶剂处理后，与熟悉物体相比，大鼠花费显著更多时间（p<0.05）探索新物体，而在亚慢性PCP处理的动物中这种效应消失。氯氮平（1.0和5.0毫克/千克）和利培酮（0.2毫克/千克）而非氟哌啶醇显著减轻了PCP诱导的损伤，使得动物与熟悉物体相比再次花费显著更多时间探索新物体（p<0.05）。这些结果支持了我们早期的工作，表明急性PCP在雌性大鼠中诱导了强烈的物体识别缺陷。氯氮平和利培酮而非氟哌啶醇显示出逆转亚慢性PCP诱导的缺陷的功效，这表明该测试对于评估改善精神分裂症认知缺陷症状的疗效可能具有一定的有效性。
