The effect of atypical and classical antipsychotics on sub-chronic PCP-induced cognitive deficits in a reversal-learning paradigm
The effect of atypical and classical antipsychotics on sub-chronic PCP-induced cognitive deficits in a reversal-learning paradigm
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DOI：
10.1016/j.bbr.2006.01.019
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发表时间：
2006-05-15
影响因子：
2.7
通讯作者：
Neill, JC
中科院分区：
文献类型：
--
作者：
Abdul-Monim, Z;Reynolds, GP;Neill, JC
苯环利定（PCP）是一种NMDA拮抗剂，已被证明可以模仿精神分裂症的某些方面，包括阳性、阴性和认知症状。该实验室先前的研究表明，急性PCP给药后存在选择性的反向学习缺陷，这种缺陷可以通过非典型抗精神病治疗而不是经典抗精神病治疗来减轻。然而，急性PCP在许多精神分裂症患者中观察到的慢性精神病和持续认知缺陷的建模方面存在局限性。因此，本研究的目的是使用先前建立的操作性反向学习程序，在较长时间内检查PCP引起的认知缺陷。此外，比较了非典型抗精神病药物氯氮平、齐拉西酮和奥氮平与经典抗精神病药物氟哌啶醇和氯丙嗪对亚慢性PCP缺陷的逆转效果。雌性兜帽李斯特大鼠被训练为使用操作性反向学习范式对食物做出反应。当动物达到90%的正确反应标准时，每天两次给予PCP （2mg /kg）或对照药，连续7天，7天后对其认知能力进行测试。相对于任务的初始阶段，PCP在逆转阶段诱发了显著的损伤。急性齐拉西酮（2.5 mg/kg）、奥氮平（1.5 mg/kg）和氯氮平（5 mg/kg）在逆转期显著减弱亚慢性PCP引起的损伤。与这些作用形成鲜明对比的是，急性给药氟哌啶醇（0.05 mg/kg）和氯丙嗪（2 mg/kg）未能显著逆转pcp诱导的认知障碍。这些数据清楚地表明，亚慢性PCP会产生持久的认知缺陷，非典型抗精神病药物而非经典抗精神病药物会显著减轻这种影响。(C) 2006 Elsevier B.V.版权所有
Phencyclidine (PCP), an NMDA antagonist, has been shown to mimic some aspects of schizophrenia including positive, negative and cognitive symptoms. Previous studies in this laboratory have shown a selective reversal-learning deficit following acute PCP administration, a deficit that is attenuated by atypical, but not classical, antipsychotic treatment. However, acute PCP has limitations for modelling the chronic psychotic illness and persistent cognitive deficits observed in many schizophrenic patients. Therefore, the aim of this study was to examine the cognitive deficit induced by PCP over a longer term using a previously established operant reversal-learning procedure. Moreover, the efficacy of the atypical antipsychotics clozapine, ziprasidone and olanzapine to reverse the sub-chronic PCP deficit was compared with that of the classical antipsychotics, haloperidol and chlorpromazine. Female hooded-Lister rats were trained to respond for food using an operant reversal-learning paradigm. When animals achieved criterion of 90% correct responding they were treated with PCP (2 mg/kg) or vehicle twice daily for 7 days, and 7 days later tested for their cognitive ability. PCP induced a significant impairment in the reversal phase relative to the initial phase of the task. Acute ziprasidone (2.5 mg/kg), olanzapine (1.5 mg/kg) and clozapine (5 mg/kg) produced a significant attenuation of the impairment induced by sub-chronic PCP in the reversal phase. In marked contrast to these effects, acute administration of the classical agents haloperidol (0.05 mg/kg) and chlorpromazine (2 mg/kg) failed to significantly reverse the PCP-induced cognitive impairment. These data clearly demonstrate that sub-chronic PCP produces enduring and persistent cognitive deficits, effects that are significantly attenuated by atypical but not classical antipsychotics. (C) 2006 Elsevier B.V. All rights reserved.