A conceptual and practical guide to the behavioural evaluation of animal models of the symptomatology and therapy of schizophrenia

Schizophrenia is a chronic debilitating brain disorder characterized by a complex set of perceptual and behavioural symptoms that severely disrupt and undermine the patient's psychological well-being and quality of life. Since the exact disease mechanisms remain essentially unknown, holistic animal models are indispensable tools for any serious investigation into the neurobiology of schizophrenia, including the search for remedies, prevention of the disease and possible biological markers. This review provides some practical advice to those confronted with the task of evaluating their animal models for relevance to schizophrenia, a task that inevitably involves behavioural tests with animals. To a novice, this challenge not only is a technical one but also entails attention to interpretative issues concerning validity and translational power. Here, we attempt to offer some guidance to help overcome these obstacles by drawing on our experience of diverse animal models of schizophrenia based on genetics, strain difference, brain lesions, pharmacological induction and early life developmental manipulations. The review pays equal emphasis to the general (theoretical) considerations of experimental design and the illustration of the problems related to critical test parameters and the data analysis of selected exemplar behavioural tests. Finally, the individual differences of behavioural expression in relevant tests observed in wild-type animals might offer an alternative approach in order to explore the mechanism of schizophrenia-related behavioural dysfunction at the molecular, cellular and structural levels, all of which are of more immediate relevance to cell and tissue research.