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Advancing rodent models of the behaviours and the neurobiological pathology associated with schizophrenia

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Advancing rodent models of the behaviours and the neurobiological pathology associated with schizophrenia

Madularu, Dan (2014) Advancing rodent models of the behaviours and the neurobiological pathology associated with schizophrenia. PhD thesis, Concordia University.

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Abstract

Schizophrenia is a psychiatric illness affecting roughly 1% of the population worldwide. The symptomatology is generally classified in terms of the enhancement or absence of otherwise normally-functioning features, and has been partially recreated in rodents and non-human primates for research purposes. The overarching goal of this thesis is to address some of the shortcomings of rat models of the behaviours and the neurobiological pathology associated with schizophrenia. Specifically, we examined the effects of estradiol on dopamine release to address the potential role of sex differences in schizophrenia development and response to treatment. Furthermore, we explored the effects of prenatal glutamatergic blockade on cognition and locomotor activity at two different stages in rat adult development. Finally, we investigated the involvement of prefronto-cortical dopamine transmission on working memory, a cognitive function disrupted in schizophrenia. When paired with estradiol, chronic haloperidol treatment was effective in blocking the hyperlocomotor-inducing effects of amphetamine, supporting clinical findings. Although we attributed this effect, in part, to dopamine transmission within the nucleus accumbens, supplementary studies offer a complete map of possible estradiol-dopamine interactions within the central nervous system. In an effort to further investigate the developmental and glutamatergic aspect of schizophrenia, we found that prenatal glutamatergic blockade results in impairments similar to those seen in other animal models, as well as patients with schizophrenia. In investigating the role of prefronto-cortical dopamine transmission vis-a-vis of working memory function in the rat, we found that working memory as measured by a delay-non-match to place task, is not driven by prefronto-cortical dopamine transmission.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Thesis (PhD)
Authors:Madularu, Dan
Institution:Concordia University
Degree Name:Ph. D.
Program:Psychology
Date:15 December 2014
Thesis Supervisor(s):Brake, Wayne and Mumby, Dave
ID Code:979602
Deposited By: DAN MADULARU
Deposited On:16 Jul 2015 15:42
Last Modified:18 Jan 2018 17:49
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