Date of Award

2025

Embargo Period

3-14-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

College

College of Graduate Studies

First Advisor

Jennifer A. Rinker

Second Advisor

L. Judson Chandler

Abstract

Learned fear responses are acquired through the identification and association of threatening stimuli with aversive outcomes. Fear responding and the proper maintenance of defensive behaviors is integral to survival. However, without the homeostasis of such systems, fear responses can become maladaptive and lead to dysregulated behavioral responding. Psychological conditions such as alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) often lead to impairments in fear learning, deficits in fear memory, and heightened fear responses. While there are clear sex differences in the prevalence of both AUD and PTSD, development of either disorder increases the risk for comorbid AUD/PTSD, leading to exacerbated symptomology of both disorders. The experiments in this dissertation focused on the impact of stress, alcohol, or the combination of these two variables on fear learning and responding in male and female rats. As threat response strategies often diverge between the sexes, both passive and active fear behavior paradigms were utilized in these studies to probe for sex differences in fear-related behaviors.

In Chapter 2, male and female Wistar rats were subjected to chronic intermittent ethanol (CIE) vapor exposure, single-prolonged stress (SPS), or both before Pavlovian fear conditioning. The results from these experiments highlight baseline sex differences present in Pavlovian fear conditioning and impairments in fear renewal in males and females as a result of alcohol exposure and stress, respectively. Chapter 3 investigated the effects of chronic ethanol exposure on active avoidance behavior in the Platform Mediated Avoidance (PMA) task in male and female Wistar rats, which resulted in a mild impairment in extinction learning in male rats. Chapter 4 utilized in-situ fluorescent hybridization to characterize a novel population of corticotropin-releasing factor (CRF) neurons in the lateral septum (LS), as these neurons may be involved in fear responding. Overall, the data presented in this dissertation highlight divergent threat response strategies adopted by male and female rats in passive versus active fear paradigms, add to our understanding of the effects of alcohol and stress exposure on fear behavior, and explore novel cell populations that may be responsible for these behavioral effects.

Rights

Copyright is held by the author. All rights reserved.

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