Geyer M A
Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0804, USA.
Neurotox Res. 2008 Aug;14(1):71-8. doi: 10.1007/BF03033576.
Animal models have long been used to explore hypotheses regarding the neurobiological substrates of and treatments for psychiatric disorders. Early attempts to develop models that mimic the entirety of the diagnostic syndromes in psychiatry have evolved into more appropriate efforts to model specific symptoms. Such an approach reflects the facts that even in patients, clinical symptoms transcend diagnostic categories, and the specific etiologies of psychiatric disorders are unknown. An animal model can only be identified adequately by specifying both the manipulation (drug, lesion, strain) used to induce abnormalities and the measure(s) used to characterize them. A wide range of pharmacological, lesion, and developmental manipulations have been combined with various measures of information processing to develop useful animal models that parallel human tests. Prepulse inhibition of startle, event-related potential (ERP) measures of auditory gating, and Cambridge neuropsychological test automated battery (CANTAB) measures of cognition are examples of measures that can be used in both rodents and humans and that are robustly altered in both psychiatric disorders and animals manipulated with appropriate drugs or lesions. The further development of cross-species models is critically important, given the new opportunities for the development and registration of specific treatments for the cognitive disorders of schizophrenia that are not ameliorated by available drugs. In moving beyond the focus on psychotic symptoms to the cognitive symptoms of schizophrenia, animal models that do not involve manipulations of dopamine D(2) receptors but that do utilize information processing measures that are correlated with cognitive disturbances are receiving increased attention. Here, selected examples of how cross-species measures of psychiatric disorders are developed and validated are discussed. Specific animal paradigms that parallel the specific domains of cognition that are altered in schizophrenia provide one focus of the review. Another focus includes efforts to develop new human models of psychiatric symptoms that are designed to parallel existing tests used in rodents.
长期以来，动物模型一直被用于探索有关精神疾病的神经生物学基础和治疗方法的假说。早期试图开发模拟精神病学中整个诊断综合征的模型，已演变成更合适的对特定症状进行建模的努力。这种方法反映了这样的事实，即即使在患者中，临床症状也超越了诊断类别，而且精神疾病的具体病因尚不清楚。只有通过明确用于诱发异常的操作（药物、损伤、品系）和用于表征异常的测量方法，才能充分确定动物模型。广泛的药理学、损伤和发育操作已与各种信息处理测量方法相结合，以开发出与人类测试相似的有用动物模型。惊吓前脉冲抑制、听觉门控的事件相关电位（ERP）测量以及认知的剑桥神经心理测试自动成套系统（CANTAB）测量，都是可用于啮齿动物和人类且在精神疾病以及用适当药物或损伤处理的动物中均有显著改变的测量方法的例子。鉴于有新的机会开发和注册针对精神分裂症认知障碍的特定治疗方法，而现有药物对此类障碍并无改善作用，跨物种模型的进一步发展至关重要。在从关注精神症状转向关注精神分裂症的认知症状的过程中，不涉及多巴胺D(2)受体操作但利用与认知障碍相关的信息处理测量方法的动物模型正受到越来越多的关注。在此，将讨论跨物种精神疾病测量方法如何开发和验证的选定示例。与精神分裂症中改变的特定认知领域相似的特定动物范式是综述的一个重点。另一个重点包括努力开发旨在与啮齿动物中使用的现有测试相似的精神症状新人类模型。
