Animal models for the negative symptoms of schizophrenia.

Negative or defect symptoms refer to a reduction in normal functioning. In schizophrenia, negative symptoms encompass, among others, anhedonia, flat affect, avolition and social withdrawal. These symptoms have been found to be particularly prominent in the more chronic phase of the illness and seem to be virtually insensitive to current antipsychotic treatment. This review focuses on the possibilities and limitations of animal models for the negative symptoms of schizophrenia. Following a review of the negative symptoms in schizophrenia, attention is focused on the two symptoms most often modelled in animals - anhedonia and social withdrawal. We then look at the important question of how to model schizophrenic pathology in animals. Since the exact pathology is still far from clear, most efforts have in the past concentrated on using psychotomimetic drugs such as amphetamine or phencyclidine. The recently accumulated knowledge that schizophrenia probably results from disturbances in the normal development of the brain has led to a surge of new animal models in which the long-term consequences of early manipulations are investigated. However, so far these models have predominantly concentrated on the positive rather than the negative symptoms of schizophrenia. The last part of this review is dedicated to the question of validation of animal models for anhedonia and social withdrawal. The general conclusion is that very few models have so far been adequately tested. The lack of currently effective treatment further hampers the study of such validation.