PhD Exit Seminar – Aya Sasaki (Erb Lab)

PhD Exit Seminar

Friday October 7^th, 1:45 pm – Earth Sciences Centre, Rm. 3056

Aya Sasaki (Erb lab)

“Influence of maternal high fat diet, stress and cocaine on neural mechanisms of reward and anxiety in rat offspring“

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, maternal HFD effects on offspring phenotype in stress-related brain regions were examined. 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 (tyrosine hydroxylase and corticotropin-releasing factor) were upregulated in HFD offspring, suggesting that maternal HFD alters neural systems underlying related processes. Second, the role of maternal HFD on offspring phenotype following chronic cocaine exposure was investigated. 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, the role of maternal HFD and maternal stress on offspring phenotype given acute cocaine exposure was investigated. 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 D1 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.