Thesis
SEX DIFFERENCES IN THE NEURAL CIRCUITS THAT PREDICT ALCOHOL DEPENDENCE
Washington State University
Master of Science (MS), Washington State University
05/2024
DOI:
https://doi.org/10.7273/000006941
Abstract
Although neurobiological mechanisms underlying alcohol use and dependence have been extensively researched, mechanisms explaining sex differences in alcohol drinking are poorly understood. The cortical-striatal circuit plays a key role in the development of alcohol dependence, and it has previously been shown that oscillations from these regions predict drinking in non-dependent male rats, but not in female rats. Since women are more likely to report using alcohol for negative reinforcement reasons and are more sensitive to stress-induced relapse, we hypothesized that stress-related neural circuits may contain more information predictive of female drinking. To test this, we determined whether cortical, striatal, and/or limbic oscillations during alcohol self-administration would distinguish between dependent and non-dependent rats in a sex-specific manner. Male and female Sprague-Dawley rats were trained to self-administer 10% alcohol before implanting bilateral electrodes targeting the infralimbic medial prefrontal cortex (mPFC), nucleus accumbens shell (NAcSh), and central nucleus of the amygdala (CeA). Then, half of the rats were exposed to four weeks of chronic intermittent alcohol (CIA) vapor (14 hours on/10 hours off) to induce dependence. After dependence was established and during acute withdrawal (approximately 7 hours after the vapor turns off), local field potentials (LFPs) were recorded from the mPFC, NAcSh, and CeA during another round of self-administration sessions. Using an unbiased machine learning approach, we built predictive models to determine whether oscillations could distinguish CIA-exposed from control rats in both sexes. Overall, female rats self-administered more alcohol than males. CIA exposure increased alcohol self-administration in both sexes, but to a larger extent in males. Preliminary analysis revealed that NAcSh and mPFC LFPs best predict CIA exposure in males, while CeA and mPFC oscillations best predict CIA exposure in females. These data provide support for sex-specific neurobiological correlates of dependence, which contributes to our understanding of sex differences in alcohol misuse.
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Details
- Title
- SEX DIFFERENCES IN THE NEURAL CIRCUITS THAT PREDICT ALCOHOL DEPENDENCE
- Creators
- Kelly A. Hewitt
- Contributors
- Angela M Henricks (Chair)Carrie Cuttler (Committee Member)Kristen Delevich (Committee Member)Rebecca M Craft (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Psychology
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 64
- Identifiers
- 99901124819401842
- Language
- English
- Resource Type
- Thesis