Neural Effects of Weekly Binge Alcohol: Sex Differences?

dc.contributor.advisorLeasure, J. Leigh
dc.contributor.committeeMemberKosten, Therese A.
dc.contributor.committeeMemberRodgers, Shaefali P.
dc.contributor.committeeMemberNixon, Kimberly
dc.creatorWest, Rebecca
dc.date.accessioned2020-01-03T06:08:58Z
dc.date.available2020-01-03T06:08:58Z
dc.date.createdDecember 2019
dc.date.issued2019-12
dc.date.submittedDecember 2019
dc.date.updated2020-01-03T06:08:58Z
dc.description.abstractIn the U.S., 1/6 of adults report binge drinking about 4 times a month. There is also mounting evidence indicating that females may be more vulnerable to the neurotoxic effects of ethanol than males. Using a novel model of weekly binge ethanol exposure, we hypothesized that cellular damage would be greater and detectable earlier in female rats in comparison to male rats. Adult Long-Evans rats were administered 5g/kg ethanol (or an iso-caloric control dose) via intra-gastric gavage once-weekly. Neither BEC (177 mg/dl) nor behavioral intoxication measures differed over time, indicating that tolerance did not occur. Male rats, however, acted more behaviorally intoxicated than females. Brains were collected either 4 or 6 days following the final ethanol dose, and immunohistochemically processed for mature neurons (NeuN), microglia (Iba1), neurogenesis (DCX) and cellular activation (c-Fos). Stereology was used to quantify target cell populations in the hippocampus and medial prefrontal cortex (mPFC). We showed that binge ethanol administration for 11 weeks increases partial activation of microglia in the hippocampus and causes significant dentate gyrus (DG) cell loss despite an increase in neurogenesis in female rats. After 3 and 8 weeks, binge ethanol significantly decreased the number of NeuN+ cells in the DG of male and female rats in comparison to controls. 8 weeks of binge ethanol significantly increased the total number of microglia (Iba1) and the number of partially activated microglia in the hippocampus and mPFC in males and females. Despite no noted behavioral deficits during reversal learning, binged rats had increased cellular activation in the mPFC during testing, indicating decreased neural efficiency. Additionally, 8 weeks of ethanol influenced ultrasonic vocalizations in male rats, however had no effect on female rats. Overall, these results show hippocampal cell loss and an increased inflammatory response in ethanol-vulnerable regions following repeated binge exposures in both male and female rats and showed changes in affect in male rats during behavioral testing.
dc.description.departmentPsychology, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: West, Rebecca K., Laian Z. Najjar, and J. Leigh Leasure. "Exercise-driven restoration of the alcohol-damaged brain." International review of neurobiology 147 (2019): 219-267. And in: West, Rebecca K., Jessica I. Wooden, Emily A. Barton, and J. Leigh Leasure. "Recurrent binge ethanol is associated with significant loss of dentate gyrus granule neurons in female rats despite concomitant increase in neurogenesis." Neuropharmacology 148 (2019): 272-283.
dc.identifier.urihttps://hdl.handle.net/10657/5659
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectAlcohol
dc.subjectBinge drinking
dc.subjectEthanol
dc.subjectHippocampus
dc.subjectMedial prefrontal cortex
dc.subjectMicroglia
dc.subjectSex differences
dc.titleNeural Effects of Weekly Binge Alcohol: Sex Differences?
dc.type.dcmiText
dc.type.genreThesis
thesis.degree.collegeCollege of Liberal Arts and Social Sciences
thesis.degree.departmentPsychology, Department of
thesis.degree.disciplineDevelopmental, Behavioral, and Cognitive Neuroscience
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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