Animal models of psychiatric disorders are a challenging but highly relevant issue. Most psychiatric disorders are very heterogeneous syndromes, resulting from multiple and varied causal factors and characterized by symptoms that can only be inferred with significant limitations in non-human models. As constructing a model that reproduces a whole psychiatric syndrome seems virtually impossible, researchers have tried to focus on endophenotypes, i.e., discrete traits that are more proximal to predisposing genes than the whole syndrome. These can be explored in a wide range of approaches, such as in pharmacological, lesion, and environmental models. Another challenge is to understand how genes interact with environmental factors over time to result in the syndromic phenotype. A better understanding of the subcellular mechanisms that enhance or allow brain resistance to environmental influences is required, as is a global thesis compatible with the diversity of diseases sharing similar behavioral and biological traits. With an experimental inventory of the possible causes of minor developmental failures, we may systematically explore their consequences in the adult animal and be able to decide if this will enlighten the understanding of one or another psychiatric disease.

OBJETIVO: O uso de modelos experimentais tem permitido importantes avanços no diagnóstico e na terapêutica de doenças somáticas, tais como diabetes e hipertensão. No caso da esquizofrenia, entretanto, as tentativas de modelos experimentais causaram, historicamente, pouco impacto e algum ceticismo. Estudos mais recentes, contudo, indicam que a Ciência Cognitiva aplicada ao uso de modelos pode nos ajudar na compreensão da fisiopatologia da esquizofrenia. O estudo objetivou realizar uma revisão crítica dos modelos experimentais propostos para a esquizofrenia. RESULTADOS E DISCUSSÃO: As dificuldades próprias dos modelos de esquizofrenia são a subjetividade dos sintomas, a dificuldade em reproduzi-los em animais e a complexidade clínica a ser totalizada. Fenótipo tão complexo só pode ser abordado pela separação de seus componentes (endofenótipos) e pela respectiva manipulação de seus correlatos experimentais, feita por intervenções específicas (e.g. farmacológicas, cirúrgicas, genéticas) na busca de um mecanismo comum para estes endofenótipos. A correlação entre resultados e sintomas deve apoiar-se em hipótese explanatória abrangente. Até o presente, a doença parece envolver desconexão neuronal difusa decorrente de anormalidades cerebrais sutis, de causa genética e/ou ambiental. CONCLUSÕES: A integração da informação dos modelos atualmente em uso pode contribuir de modo significativo para a compreensão da esquizofrenia.

OBJECTIVE: Diagnostic and therapy of somatic diseases like diabetes and hypertension have improved notably with the use of experimental models. For schizophrenia the proposal of a model has made little impact and even scepticism. Nevertheless the most recent studies indicate that "Cognitive Sciences" applied to specific models may help us to find out mechanisms of the disease. This article reviews the models presently under investigation for schizophrenia. RESULTS AND DISCUSSION: The difficulty to model schizophrenia results from the subjectivity of its symptoms, the difficult to reproduce them in animals and the disease complexity. Research on such a complex phenotype can only proceed by separating its components (endophenotypes) from each other and by the respective manipulation of its experimental counterparts, made by specific interventions (e.g. pharmacological, surgical, genetic), in the search of a common mechanism leading to these endophenotypes. For integrating these findings with symptoms a global explanatory theory is required. So far, the disease seems to result from a diffuse neuronal disconnection as a consequence of minor brain abnormalities with a genetic and/or environmental cause. CONCLUSIONS: An integrative approach of the diversity of models presently used may improve our understanding of schizophrenia.