- Title
- The effect of maternal immune activation and adolescent cannabinoid exposure on behaviour, neurophysiology and cognition in a rodent model of schizophrenia
- Creator
- Dunn, Ariel Louise
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2020
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Schizophrenia is a complex debilitating disorder with many genetic and environmental risk factors implicated in its aetiology. Given the disorders’ heterogeneous nature, it is unlikely that any single risk factor could produce the entire array of symptoms. Therefore, exposure to multiple risk factors during critical periods of brain development, such as prenatally or during adolescence, likely interact to produce alterations in schizophrenia. Previous epidemiological findings have demonstrated that both exposure to maternal immune activation (MIA) in the prenatal period, and adolescent cannabinoid exposure (ACE), confer an increased risk for schizophrenia later in life. Preclinical rodent models of these two manipulations alone support these epidemiological findings and exhibit a variety of behavioural and cognitive phenotypes in adulthood that mimic those occurring in schizophrenia. The aim of this thesis was to investigate the combined exposure of MIA x ACE and its effect on rat behavioural, cognitive and neurophysiological phenotypes in adulthood, and to determine if the MIA x ACE model would be a useful model mimicking cognitive and other impairments of schizophrenia. Use of a broad suite of behavioural and cognitive tasks elucidated that schizophrenia-like alterations were predominately restricted to female rats. Some synergistic MIA x ACE effects were observed, with Two-Hit females showing reduced sensorimotor gating and increased marble burying, and both male and female Two-Hit rats showing reduced early mismatch responses (MMRs). However, no changes in cognition in domains such as visual learning and memory, problem solving or working memory, were observed in Two-Hit animals. Additionally, some cognitive and behavioural effects, such as sensorimotor gating in males and progressive ratio lever pressing were reversed or ‘protected’ by MIA x ACE. This study indicates that the MIA x ACE model may be a useful tool for further examination of specific schizophrenia-related features, such as sensorimotor gating deficits or early mismatch response impairments, but is not a model well-suited for further examination of schizophrenia-related cognitive impairments. Importantly, this research has highlighted the continuing importance of including both male and female animals in preclinical models.
- Subject
- schizophrenia; cannabis; prenatal infection; animal model; neurodevelopment
- Identifier
- http://hdl.handle.net/1959.13/1429804
- Identifier
- uon:38769
- Rights
- Copyright 2020 Ariel Louise Dunn
- Language
- eng
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| View Details Download | ATTACHMENT01 | Thesis | 3 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 449 KB | Adobe Acrobat PDF | View Details Download |