Modeling the two-hit hypothesis of schizophrenia: combined neonatal stress and postnatal corticosterone in rats

Funded Activity Summary

Schizophrenia is a severe mental illness defined by a number of symptoms including hallucinations, delusions, social withdrawal and cognitive impairment. Factors very early in development have been suggested to induce an increased vulnerability to this illness. Recently, it was suggested that another major event, later in life, would be needed before vulnerable individuals would develop schizophrenia. The aim of this project is to model this two-hit hypothesis in rats. We will compare the effect of various neonatal maternal separation protocols as an early stressful event, followed by chronic treatment with the stress hormone corticosterone at various stages later in life. We will also perform a detailed anatomical study of the hippocampus of these rats. This brain area has been implicated in the development of schizophrenia in humans. We will also investigate if treatment with antipsychotic drugs can prevent or reverse behavioural and neuroanatomical changes seen in the rats. This will be the first comprehensive study to model this two-hit neurodevelopment hypothesis of schizophrenia and will provide an experimental verification of a clinical concept which is very difficult to prove in patients.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $318,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Psychiatry

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

animal models | antipsychotics | behaviour | dopamine | neurodevelopment | puberty | schizophrenia | stress

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