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dc.contributor.authorWilson, Christina Ann
dc.date.accessioned2014-06-03T19:22:23Z
dc.date.available2014-06-03T19:22:23Z
dc.date.issued2012-10en
dc.identifier.urihttp://hdl.handle.net/10675.2/318800
dc.description.abstractCognitive dysfunction is now recognized to be central to the functional disability of several neuropsychiatric disorders. However, treatment options for the management of cognitive symptoms are limited and the development of novel therapeutics has been made difficult by the lack of appropriate animal models. It has been suggested that variable prenatal stress (PNS) in rodents might be an etiologically appropriate model for some components of schizophrenia. Thus, the overall goal of this dissertation project was to conduct a comprehensive behavioral study of the model to assess face validity, and to make a preliminary assessment of its construct and predictive validity. Our results indicate that exposure to PNS results in elevated corticosterone levels following exposure to acute stress, increased aggressive behaviors, as well as increased locomotor activity and stereotypic behaviors. Further, PNS rats had altered innate fear responses to predator odor as well as impaired fear extinction. Additionally, PNS in rats was associated with impairments of sustained attention, inhibitory response control, and recognition memory all of which could be attenuated by the norepinephrine reuptake inhibitor, atomoxetine. Collectivity, these data support the premise that PNS in rodents is a valid model system for studying some behavioral components of neuropsychiatric disorders as well as their treatment.
dc.language.isoen_USen
dc.relation.urlhttp://search.proquest.com/docview/1221043597?accountid=12365en
dc.subjectAnimal Modelsen
dc.subjectNeuropsychiatric Disordersen
dc.subjectPrenatal Stressen
dc.subjectSchizophreniaen
dc.subjectCognitionen
dc.subjectNeurodevelopmenten
dc.subjectDrug Discoveryen
dc.subjectAtomoxetineen
dc.titleA Variable Prenatal Stress Paradigm as a Valid Drug Discovery Platform for Cognitive Deficits Associated with Neuropsychiatric Disordersen
dc.typeDissertationen
dc.contributor.departmentDepartment of Pharmacology and Toxicologyen
dc.description.advisorTerry, Alvin V.en
dc.description.degreeDoctor of Philosophy (Ph.D.)en
dc.description.committeeBlake, David; Bergson, Clare; Vazdarjanova, Almira; Pillai, Anil.en
html.description.abstractCognitive dysfunction is now recognized to be central to the functional disability of several neuropsychiatric disorders. However, treatment options for the management of cognitive symptoms are limited and the development of novel therapeutics has been made difficult by the lack of appropriate animal models. It has been suggested that variable prenatal stress (PNS) in rodents might be an etiologically appropriate model for some components of schizophrenia. Thus, the overall goal of this dissertation project was to conduct a comprehensive behavioral study of the model to assess face validity, and to make a preliminary assessment of its construct and predictive validity. Our results indicate that exposure to PNS results in elevated corticosterone levels following exposure to acute stress, increased aggressive behaviors, as well as increased locomotor activity and stereotypic behaviors. Further, PNS rats had altered innate fear responses to predator odor as well as impaired fear extinction. Additionally, PNS in rats was associated with impairments of sustained attention, inhibitory response control, and recognition memory all of which could be attenuated by the norepinephrine reuptake inhibitor, atomoxetine. Collectivity, these data support the premise that PNS in rodents is a valid model system for studying some behavioral components of neuropsychiatric disorders as well as their treatment.


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