Behavioral perturbations after prenatal neurogenesis disturbance in female rat

The exposure to methylazoxymethanol (MAM) at embryonic day 17 (E17) results in behavioral anomalies in male rats that mimic several features of schizophrenia, including their emergence after puberty. Given that both men and women are likely to develop this illness and that currently no animal model is validated for females, we examined the behavioral consequences of E17 MAM exposure in female rats. We compared E17 MAM- and saline-exposed female rats before and/or after puberty for spontaneous activity, alternance and spatial recognition (Y-maze), spatial learning (Morris water maze), and sensory gating using the prepulse inhibition task. MAM-exposed female rats exhibited a significant increase in spontaneous locomotor activity in a novel environment, compared to sham animals, which emerged only after puberty. They also had deficits in spontaneous alternation performance and spatial recognition in a Y-maze as well as reference memory deficits in a Morris water maze task. Lastly, MAM-exposed female rats spent significantly less time in social interaction at both pre- and post-puberty and had a deficit in prepulse inhibition of the startle reflex (PPI) at adulthood. In conclusion, the present results show that, in female rat, exposure to MAM at E17 results in a pattern of behavioral changes that, on the whole, mimic positive, negative, and cognitive dimensions of schizophrenia. E17 MAM exposure thus appears to be a valid model for schizophrenia in both males and females.