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Prenatal PolyI:C induced schizophrenia-like cognitive inflexibilities in the male, but not female, rat adult offspring

Executive functions are important cognitive processes critical for survival. Damage to the prefrontal cortex impairs executive functions, such as working memory, decision making and set-shifting. Interestingly, patients diagnosed with different psychiatric disorders are also impaired in executive functions, especially in the set-shift domain, often measured by the Wisconsin Card Sorting Task (WCST). Set-shifting is an essential cognitive process, in that it allows the individual to suppress non-reinforcing strategies and engage in new rewarding strategies. To date, little is known about the etiology of executive dysfunction in psychiatric disorders. However, some epidemiological and serological experiments have shown strong correlations between prenatal infection and the increased risk to develop psychiatric disorders in the adult offspring. One study found that schizophrenic patients pre-exposed to a prenatal infection perseverated more during the WCST, than non-pre-exposed patients. Despite these findings, there are still numerous limitations (e.g., ethical concerns) when conducting these studies. Thus, animal models are important and can further elucidate the etiology of executive dysfunctions in psychiatric disorders. Prenatal infection animal models have consistently shown that inflammation during gestation in rodents induces behavioural, anatomical and cognitive changes in the adult offspring similar to psychiatric patients. However, no studies have investigated the effects of prenatal infection on set-shifting in the adult offspring. Therefore, the present thesis examined whether prenatal treatment with PolyI:C (a viral mimetic) during middle/late gestation of the rat would induce cognitive inflexibilities (i.e., set-shifting and reversal learning in an operant based task analogous to the WCST) in the adult male and female offspring. The results showed PolyI:C male offspring perseverated during the set-shift but had fewer regressive errors during the reversal learning day. PolyI:C treated female offspring were not impaired during any of the test days; however, females were slower to respond to the lever and required more training when compared the male rats. Taken together, these results give support for prenatal infection in inducing cognitive inflexibility, by potentially altering the PFC in the adult offspring.
MS-based thesis:
Zhang, Y., Cazakoff, B. N., Thai, C. A., & Howland, J. G. (2011). Prenatal exposure to a viral mimetic alters behavioural flexibility in male, but not female, rats. Neuropharmacology, [epub ahead of print]. doi:10.1016/j.neuropharm.2011.02.022

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-07142011-120132
Date05 August 2011
CreatorsZhang, Ying
ContributorsBowen, Angela N., Kalynchuk, Lisa E., Howland, John G., Borowsky, Ron
PublisherUniversity of Saskatchewan
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://library.usask.ca/theses/available/etd-07142011-120132/
Rightsunrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.

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