Schizophrenia‐like behaviors in the offspring after maternal stress and prenatal NMDA receptor hypofunction (1144.9)

Abstract

Pharmacological animal models have been developed and used to study the neurobiological deficits most commonly associated with schizophrenia. Evidence suggests that NMDA receptor (NMDAR) activity is an integral component in the pathophysiology of the disease, because antagonizing this receptor leads to schizophrenic‐like neurophysiological alterations and behaviors. In this study we sought to determine the influence of maternal NMDAR hypofunction combined with stress in the outcome of schizophrenia‐like behaviors of the offspring. After daily prenatal injections of MK‐801 and induction of stress in female mice, pregnancy was allowed to ensue and the litter was allowed to develop to P21‐P30. Analysis of schizophrenia‐like behaviors was performed on the offspring by measuring cognition as well as anxiety and other related behaviors. Our results suggest that maternal NMDAR dysfunction together with environmental stress impact the neurodevelopmental status of the offspring. These results not only strengthen the view that NMDAR function is involved in normal brain development, but also show that changes induced prenatally can affect the brains of the offspring.