Abstract

Schizophrenia is a severe psychiatric illness characterized by positive, negative, and cognitive symptoms. The observation that the onset of clinical symptoms is often in early adulthood has led to the neurodevelopmental hypothesis which posits that schizophrenia results from altered developmental processes beginning long before onset of clinical symptoms. The present thesis aimed to evaluate two neurodevelopmental animal models of schizophrenia-like behaviours. Chapter one explored the epidemiological association between maternal infection and schizophrenia by using a well-validated animal model of maternal viral infection. Pregnant Wistar rats were injected with the viral mimic polyriboinosinic-polyribocytidilic acid (poly I:C) and juvenile and adult offspring were assessed for altered novel object preference (NOP), sensitivity to the locomotor-activating effects of amphetamine, and deficits in preattentive sensorimotor gating mechanisms. Our findings suggest that prenatal poly I:C did not result in the expected behavioural deficits in adulthood. Our findings challenge the robustness of the poly I:C model. In chapter two, we examined behavioural and neurochemical consequences of prenatal blockade of the glutamate receptor, N-methyl-D-aspartate (NMDA), in juvenile and adult offspring. Pregnant Long-Evans rats received daily injections of saline or the NMDA receptor antagonist, MK-801. Offspring were exposed to a battery of behavioural tasks. The most dramatic of our findings were the altered NOP, hyposensitivity to MK-801 challenges, and deficits in cognitive flexibility observed in the adult male offspring. Although sometimes contrary to our hypotheses, the overall pattern of our results suggest that prenatal NMDA receptor blockade disrupted normal brain development and induced important behavioural deficits in adulthood.