Date of Award

2017

Embargo Period

8-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

College

College of Graduate Studies

First Advisor

L. Judson Chandler

Second Advisor

Howard C. Becker

Third Advisor

Justin T. Gass

Fourth Advisor

William C. Griffin

Fifth Advisor

John J. Woodward

Abstract

The prefrontal cortex (PFC) is critical for executive functions that underlie behavioral flexibility, but is especially vulnerable to environmental insults during development, which concludes after adolescence. Adolescence is a time of neural development, and is marked by increased risk-taking and impaired judgment. Adolescence is often associated with engagement in risky behaviors such as experimentation with drugs of abuse, including alcohol. Alcohol is particularly damaging to the PFC, and leads to negative impacts on executive functions. Traumatic stress has also been shown to negatively impact executive functions, and alcohol use and stress disorders frequently occur co-morbidly. Additionally, deficits in executive functions following adolescent alcohol or traumatic stress exposure in rats may differentially affect different strains of rats. This dissertation addressed the overarching hypothesis that binge-like adolescent alcohol (AIE) and a model of traumatic stress (SPS) negatively impact executive functions in adulthood, and that two strains of rats (Long-Evans, LE, and Sprague-Dawley, SD) may respond differentially to these exposures. First, the effects of AIE and SPS in adulthood on probabilistic reversal learning (PRL) were examined. AIE impaired discrimination learning with probabilistic reinforcement in LE rats on day one of the PRL task, and led to decreased reward and negative feedback sensitivity in SD rats over extended testing. SPS exposure following AIE led to increased negative feedback and reward sensitivity in LE rats. The second component of this dissertation addressed the effects of AIE and SPS on the probabilistic decision-making task. AIE led to increased choice latency and impaired mastery of the task in SD rats during initial training sessions. SPS exposure following AIE led to decreased risky choice compared to SPS exposure alone in SD rats. The third component of this dissertation addressed the effects of AIE and SPS on fear-related behaviors. AIE and SPS exposure led to faster acquisition of associative fear conditioning in LE rats, and increased resistance to extinction. Taken together, this dissertation demonstrates that AIE leads to persistent deficits in behavioral flexibility in adulthood, and that SPS exacerbates these deficits.

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