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Enhanced Female Vulnerability to Cocaine Self-Administration

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title
Enhanced Female Vulnerability to Cocaine Self-Administration
author
Mauterer, Madelyn Irie
abstract
Over 5 million people in the United States report past year cocaine use annually; however, only approximately 500,000 of these individuals will progress to cocaine use disorder (CUD). This indicates that, like all drugs of abuse, not all cocaine users are susceptible to the development of CUD. Individual differences in the progression of substance abuse are well documented in clinical and preclinical literature. Biological sex is one such source of individual variability across drugs of abuse, especially cocaine. Specifically, despite lower rates of cocaine use relative to men, women show a telescoped progression from initial cocaine use the onset of CUD as well as more severe overall symptoms. Though enhanced vulnerability to CUD in females has been demonstrated in both clinical and preclinical studies, our understanding of the influence of biological sex and the underlying neurobiological mechanisms remains incomplete. We therefore first sought to determine how female vulnerability presented during early cocaine taking – specifically during initiation of cocaine use. To this end, we examined how innate neurobiology and the estrous cycle can influence acquisition of cocaine self-administration behavior. Here, we show that females in the estrus stage of the estrous cycle exhibit the greatest acquisition behavior as well as increased dopamine terminal sensitivity to cocaine, with the greatest effect being at the dopamine transporter. Building on these findings, we further investigated female vulnerability to cocaine taking during later stage CUD-like behavior. To this end, we assessed changes in female motivated behavior following extended access cocaine taking using the behavioral economics derived threshold protocol. In this way we found that females exhibit greater motivation for cocaine after extended access cocaine taking relative to baseline motivation. Ultimately, this body of work seeks to uncover novel intricacies of female vulnerability to cocaine taking behavior and underlying neurobiology while building on the foundational research that has already been conducted in the field. While great efforts continue to be made to treat CUD, this research further emphasizes the importance of identifying innate vulnerabilities that predispose individuals to the development of CUD. This will ultimately allow for the identification of risk factors that can be targeted to prevent the progression of CUD rather than attempting to treat or cure an already present disease state.
subject
Behavioral Economics
Cocaine
Dopamine
Female
Self-administration
Sex Differences
contributor
Jones, Sara R (committee chair)
Martin, Thomas J (committee member)
Kishida, Kenneth T (committee member)
Lynch, Wendy J (committee member)
McCool, Brian A (committee member)
Nader, Michael A (committee member)
date
2022-09-17T08:35:41Z (accessioned)
2022-09-17T08:35:41Z (available)
2022 (issued)
degree
Neuroscience (discipline)
identifier
http://hdl.handle.net/10339/101250 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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