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 a ffect, avolition and social withdrawal. These symptoms have been found to b e 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 nega tive symptoms of schizophrenia. Following a review of the negative symptoms in schizophrenia, attention is focused on the two symptoms most often mode lled in animals - anhedonia and social withdrawal. We then look at the impo rtant question of how to model schizophrenic pathology in animals. Since th e exact pathology is still far from clear, most efforts have in the past co ncentrated on using psychotomimetic drugs such as amphetamine or phencyclid ine. The recently accumulated knowledge that schizophrenia probably results from disturbances in the normal development of the brain has led to a surg e of new animal models in which the long-term consequences of early manipul ations are investigated. However, so far these models have predominantly co ncentrated on the positive rather than the negative symptoms of schizophren ia. The last part of this review is dedicated to the question of validation of animal models for anhedonia and social withdrawal. The general conclusi on is that very few models have so far been adequately tested. The lack of currently effective treatment further hampers the study of such validation. (C) 2000 Lippincott Williams & Wilkins.