Floresco Stan B, Geyer Mark A, Gold Lisa H, Grace Anthony A
Department of Psychology, University of British Columbia, Vancouver, Canada.
Schizophr Bull. 2005 Oct;31(4):888-94. doi: 10.1093/schbul/sbi041. Epub 2005 Aug 3.
Animal models are an essential initial phase in the discovery of novel drugs to treat psychiatric disorders. At the sixth Measurement and Treatment Research to Improve Cognition in Schizophrenia conference, "New Approaches to Assessing and Improving Cognition in Schizophrenia," a discussion group was formed to address issues related to the development of predictive animal models of cognition that may be used as preclinical assays for putative cognitive enhancers. We identified 2 complementary approaches used to model cognitive impairments in animals. First, basic lesion/pharmacological models provide information about the particular neural substrates that may underlie different types of cognitive deficits found in schizophrenia. Findings from these studies can be mapped onto the second, more elaborate and etiologically relevant neurodevelopmental models of the disorder to ascertain which cognitive systems may be altered by early developmental insults. Particular attention must be given to the types of animal tasks used, in order to relate directly to the cognitive domains that are affected in schizophrenia patients. Importantly, the validation and standardization of the methodologies used in these preclinical assays would require the establishment of a preclinical trials network, serving as a counterpart to the recently established Treatment Units for Research on Neurocognition and Schizophrenia. The need to validate specific approaches to assess cognitive functions relevant to schizophrenia could be satisfied by a concerted effort enabled by a new funding directive from the National Institute of Mental Health with the explicit purpose of facilitating research on these models and assessing novel drug therapies that may be used to ameliorate the cognitive deficits in schizophrenia.
动物模型是发现治疗精神疾病新药的重要初始阶段。在第六届改善精神分裂症认知的测量与治疗研究会议“评估和改善精神分裂症认知的新方法”上，成立了一个讨论小组，以探讨与开发认知预测动物模型相关的问题，这些模型可作为推定认知增强剂的临床前检测方法。我们确定了两种用于模拟动物认知障碍的互补方法。首先，基本损伤/药理学模型提供了有关精神分裂症中发现的不同类型认知缺陷可能潜在的特定神经基质的信息。这些研究的结果可以映射到第二种更精细且与病因相关的该疾病神经发育模型上，以确定哪些认知系统可能会因早期发育损伤而改变。必须特别关注所使用的动物任务类型，以便直接关联到精神分裂症患者受影响的认知领域。重要的是，这些临床前检测中使用的方法的验证和标准化将需要建立一个临床前试验网络，作为最近成立的神经认知与精神分裂症研究治疗单位的对应机构。美国国立精神卫生研究所的一项新资助指令明确旨在促进对这些模型的研究并评估可能用于改善精神分裂症认知缺陷的新型药物疗法，通过共同努力可以满足验证评估与精神分裂症相关认知功能的特定方法的需求。
