371. Translational relevance of the MAM model in schizophrenia: a systematic review of behavioral and neurobiological findings
Abstract Background Schizophrenia is a severe mental illness with neurodevelopmental origins, typically manifesting in early adulthood and characterized by diverse alterations in cognition, perception, and behavior. Despite extensive research, the underlying mechanisms of the disorder remain only partially understood. While animal models have been instrumental in attempting to bridge this knowledge gap, many existing models fail to replicate the full clinical complexity of the disorder. Aims & Objectives The objective of this study is to evaluate the methylazoxymethanol acetate (MAM) model, which distinguishes itself by its ability to capture key neurodevelopmental and behavioral phenotypes of schizophrenia. Specifically, this review aims to validate the MAM model as a robust tool for translational research to better understand the disorder's pathophysiology. Method A systematic review following CAMARADES guidelines identified studies on the gestational MAM rodent model via PubMed, and Web of Science. Data on behavioral, physiological, histological, genetic, and pharmacological —as well as experimental protocols—were extracted from eligible studies. Results Out of 203 articles, 53 original articles met inclusion criteria. These studies consistently reported schizophrenia-like behavioral deficits in MAM-exposed offspring (sensorimotor gating impairment, reduced social interaction, and cognitive inflexibility), neurophysiological abnormalities (mesolimbic dopaminergic hyperactivity and cortical glutamatergic hypoactivity), histopathological changes (loss of parvalbumin-positive interneurons and altered dendritic morphology), gene expression dysregulation, and strong pharmacological responsiveness to antipsychotic treatment. These convergent findings confirm the model’s translational relevance. Discussion & Conclusions The MAM model robustly recapitulates key features of schizophrenia, providing a translational platform to probe its pathophysiology and identify novel therapeutic treatment targets. However, inconsistent study designs and populations limits cross-study comparability. Establishing standardized experimental criteria and incorporating longitudinal studies will be critical to fully harness this model’s utility for research and drug development.