The role of rodent models in the discovery of new treatments for schizophrenia: updating our strategy.
The role of rodent models in the discovery of new treatments for schizophrenia: updating our strategy.
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DOI：
10.1093/schbul/sbq106
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发表时间：
2010-11
影响因子：
6.6
通讯作者：
H. Moore
中科院分区：
文献类型：
--
作者：
H. Moore
精神分裂症临床前研究中使用的策略已经从专注于现有抗精神病药物或拟精神病药物药理学的实验发展到对精神分裂症中受影响的神经行为系统的药理学调节的更广泛研究。作为另一种方法，神经发育（包括遗传）操纵已越来越多地用于模拟疾病风险因素或诱发精神分裂症相关的神经病理学。在绝大多数这些模型中，行为测试范式用于测试药物或发育操作对精神分裂症中假设受影响的心理、认知和情感过程的影响。术语“精神分裂症动物模型”现在适用于这些策略的任何组合。动物建模策略的扩展导致了识别新的神经机制的重大创新，这些机制不仅可能导致精神病，而且可能导致精神分裂症的认知和阴性症状。然而，在发现真正新颖的治疗靶点方面的创新成本之一是假阳性的风险更高-药物在动物模型中显示出希望，但在临床试验中却没有。本评论的目的是首先提供一个简短的历史和概念化的啮齿动物模型在临床前研究，然后检查要解决的问题，以提高动物模型的预测能力，在确定新的治疗目标，并最终，新的有效治疗精神分裂症。
The strategies used in preclinical research in schizophrenia have evolved from experiments focused on the pharmacology of existing antipsychotic or psychotomimetic drugs to the broader study of pharmacological modulation of the neurobehavioral systems affected in schizophrenia. As an additional approach, neurodevelopmental, including genetic, manipulations have become increasingly used to model disease risk factors or to induce schizophrenia-relevant neuropathology. In the vast majority of these models, behavioral testing paradigms are used to test the effects of the drugs or developmental manipulations on psychomotor, cognitive and affective processes hypothesized to be affected in schizophrenia. The term "animal model of schizophrenia" is now applied to any combination of these strategies. The expansion in animal modeling strategies has led to significant innovation in identifying novel neural mechanisms that may contribute not only to psychosis but also to the cognitive and negative symptoms of schizophrenia. Yet one cost of innovation in the discovery of truly novel treatment targets is a higher risk for false positives--drugs that have shown promise in animal models but not in clinical trials. The goals of this commentary are to first provide a brief history and conceptualization of rodent models in preclinical research and then examine the issues to be addressed in order to increase the predictive power of animal models in the identification of new treatment targets and, ultimately, new effective treatments for schizophrenia.