Item – Theses Canada

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OCLC number
1333979991
Link(s) to full text
LAC copy
Author
Sasaki, Aya.
Title
Influence of Maternal High Fat Diet, Stress and Cocaine on Neural Mechanisms of Reward and Anxiety in Rat Offspring.
Degree
Ph.D. -- University of Toronto, 2017.
Publisher
[Toronto, Ontario] : University of Toronto, 2017
Description
1 online resource
Abstract
Maternal obesity has important health consequences for the mother and her offspring. Experiments presented in this dissertation explored the role of maternal overnutrition with a high fat diet (HFD) on several aspects of offspring phenotype: reward- and stress-related behaviours, the endocrine stress response, and associated neural gene expression. First, I examined maternal HFD effects on offspring phenotype in stress-related brain regions. Maternal HFD was associated with altered expression of stress-related genes, a heightened endocrine stress response and increased anxiety behaviour in adult offspring. Genes central to stress and drug addiction (TH and CRF) were upregulated in HFD offspring, suggesting that maternal HFD alters neural systems underlying related processes. Second, I investigated the role of maternal HFD on offspring phenotype following chronic cocaine exposure. Maternal HFD increased anxiety in saline-treated control females, reduced anxiety in cocaine-treated females, but did not interact with cocaine-primed locomotor activity or neural gene expression. These findings suggest that maternal HFD modulates offspring anxiety behavior with chronic cocaine exposure. Third, I investigated the role of maternal HFD and maternal stress on offspring phenotype given acute cocaine exposure. Maternal HFD did not interact with cocaine at the level of behavior or gene expression. However, there was an increase in locomotor activity in males exposed to maternal HFD, and with maternal stress at a high dose of cocaine. These findings suggest that, overall, maternal HFD and stress increase cocaine-induced locomotor activity in offspring through common but not identical neural mechanisms. Finally, in parallel I investigated the role of pre-gestational cocaine on offspring phenotype, and demonstrated an effect on the locomotor activating effects of cocaine in adult male offspring, as well as dopamine receptor 1 expression in the medial prefrontal cortex. These findings suggest increased sensitivity to cocaine in the male offspring of mothers given pre-gestational cocaine. The collective findings are discussed within a framework of maternal influences on cocaine sensitivity in offspring, wherein maternal HFD and pre-gestational cocaine confer increased sensitivity of stress- and reward-related responses in offspring.
Other link(s)
tspace.library.utoronto.ca
hdl.handle.net
Subject
anxiety
gene expression
hpa stress axis
maternal overnutrition
psychomotor activity