ABSTRACT
Introduction Perhaps no other topic in behavioural neuroscience or psychopharmacology has been so controversial or maligned; yet the validity of animal models of schizophrenia remains one of the most important and contemporary issues in the entire field of translational and clinical neuroscience. This paradoxical position has arisen partly from the reappraisal of the significance of the cognitive deficits in schizophrenia and from a perception of the need to pursue new hypotheses concerning the understanding of the positive and negative symptoms of this disorder, as well as their neural and neurochemical substrates. When considering the concept of “animal models” of human neurological or neuropsychiatric disorders, there are several considerations that need to be taken into account, particularly in the case of schizophrenia. Animal “models” of neurodegenerative diseases such as Huntington’s and Alzheimer’s diseases will ultimately have been indispensable for defining the causal role of specific forms of molecular pathology and also for assessment of new therapeutic strategies based, for example, on neuroprotection. Some of these diseases have a clear genetic basis, and may even be monogenic in nature; hence genetic models are plausible and are also more than likely to be useful. But this is not the case in schizophrenia. Although much is known about the neurobiological correlates of the disorder, these do not include any reliable information about its molecular pathology, and, like many neuropsychiatric disorders, its genetic involvement is complex, generally depending on multiple genes, each likely to have only small effects. Thus modelling a single genetic change using transgenic preparations is unlikely to capture any of the complexity of the complex syndrome that is schizophrenia. An additional problem concerns the bizarre and subjective nature of many of the symptoms in schizophrenia such as hallucinations and delusions; it is notoriously difficult to relate such symptoms to what is likely to be observed in, for example, a murine model. Understandably, these difficulties have led to assertions that it is impossible to provide an animal model of schizophrenia.
