Miyamoto Yoshiaki, Nitta Atsumi
Department of Pharmaceutical Therapy & Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
J Pharmacol Sci. 2014;126(4):310-20. doi: 10.1254/jphs.14R02CR. Epub 2014 Nov 18.
A devastating psychiatric disorder, schizophrenia is characterized by three major symptoms, positive and negative symptoms and cognitive deficit. Almost all current therapeutic drugs for schizophrenia have efficacy for positive symptoms, and weak efficacy for negative and cognitive deficit. In particular, social withdrawal, diminished motivation, and anhedonia as the depressive aspects of negative symptoms are resistant to the treatment of antipsychotic drugs. Therefore, there is a need for development of new therapeutic drugs for negative symptoms of schizophrenia, and it is necessary to have comprehensive animal models to understand the neurobiological foundations of their symptoms. In this review, we represent the behavioral phenotypes in available animal models of schizophrenia for drug discovery, focusing on the depressive aspects of negative symptoms. We mention here animal models based on the pathology and epidemiology of schizophrenia, e.g., the pharmacological, neurodevelopmental, genetic, and gene-environment combination models. The animal models of schizophrenia are developed by various approaches and are assessed, but there are few models demonstrating negative symptoms with sensitivities to available therapeutic drugs. The development of comprehensive animal model reflecting negative symptoms and of novel compounds that can remedy them provide certain insight into the neurobiological process of schizophrenia and also point the way to a new therapeutic strategy.
精神分裂症是一种极具破坏性的精神疾病，其特征为三大症状，即阳性症状、阴性症状和认知缺陷。几乎所有目前用于治疗精神分裂症的药物对阳性症状都有效，但对阴性症状和认知缺陷的疗效较弱。特别是，作为阴性症状抑郁方面的社交退缩、动机减退和快感缺失对抗精神病药物治疗具有抗性。因此，需要开发治疗精神分裂症阴性症状的新治疗药物，并且有必要建立全面的动物模型来了解其症状的神经生物学基础。在本综述中，我们介绍了用于药物发现的现有精神分裂症动物模型中的行为表型，重点关注阴性症状的抑郁方面。我们在此提及基于精神分裂症病理学和流行病学的动物模型，例如药理学、神经发育、遗传和基因 - 环境组合模型。精神分裂症的动物模型通过各种方法开发并进行评估，但很少有模型能表现出对现有治疗药物敏感的阴性症状。反映阴性症状的全面动物模型以及能够治疗这些症状的新型化合物的开发，为精神分裂症的神经生物学过程提供了一定的见解，也为新的治疗策略指明了方向。
