Abstract
Methylazoxymethanol (MAM) treated pregnant rats at gestation day (GD) 17 has revealed itself as a valuable experimental animal model for schizophrenia. Yet, this model remains to be established in mice. In the present study, we examined behavioral, cytoarchitectural, and neurochemical changes in the offspring of MAM treated mice and validated the model’s face, construct and predictive values. We found that in contrast to a single injection of MAM to dams at GD 15, 16 or 17, its repeated administration between GD 15 and 17 led to increase in locomotor activity induced by the NMDA antagonist MK‐801, social withdrawal, short‐term memory impairment and deficit in prepulse inhibition (PPI) in the post‐pubertal offspring. Moreover, we observed a reduction in the volume of both the prefrontal cortex (PFC) and hippocampus, neuroanatomical changes in the hippocampus, and a disturbance in the dopaminergic system in the PFC. In contrast to haloperidol, clozapine, risperidone, and aripiprazole all reversed the PPI deficit in the offspring of MAM treated dams. Therefore, the treatment of pregnant mice with MAM during GD 15‐17 offers a new method to study neurobiological mechanisms involved in the pathogenesis of schizophrenia.
