Dysregulation of Dopamine Systems in a Developmental Disruption Model of Schizophrenia: Implications for Pathophysiology, Treatment, and Prevention

Clinical observations, postmortem work, and neuroimaging have fostered hypotheses on the etiology, pathology, psychology, and progression of schizophrenia. However, animal models are indispensable tools for testing and expanding these hypotheses rigorously. Here we review the methylazoxymethanol (MAM)-17 neurodevelopmental animal model of schizophrenia in which gross brain abnormalities observed in schizophrenia can be reliably mimicked by exposure to MAM in the rat on gestational day 17. In establishing the validity of this model, we summarize the rationale for approaching schizophrenia as a neurodevelopmental disorder, for using the MAM compound, and the schizophrenia-like abnormalities that the model reproduces. Work in this model has already led to the generation of unifying hypotheses on network dysfunction in schizophrenia, especially the relationship between anomalous hippocampal activity and dopamine dysregulation. Looking forward, the MAM-17 is an important animal model in which the critical neurodevelopmental events underlying the adolescent onset of this disorder may be elucidated and novel treatments may be tested and compared with currently available antipsychotics.