Date Approved

6-30-2025

Embargo Period

6-30-2025

Document Type

Dissertation

Degree Name

Ph.D. Molecular Cell Biology & Neuroscience

Department

Cell Biology and Neuroscience

College

Rowan-Virtua School of Translational Biomedical Engineering & Sciences

Advisor

Daniel Chandler, Ph.D.

Committee Member 1

Benjamin Rood, Ph.D.

Committee Member 2

Jessica Loweth, Ph.D.

Committee Member 3

Elizabeth West-Niedringhaus, Ph.D.

Committee Member 4

Daniel Manvich, Ph.D.

Disciplines

Medical Sciences | Medicine and Health Sciences | Neurosciences

Abstract

Stress is a physiological state of altered neuroendocrine signaling and heightened indices of behavioral vigilance and arousal in response to threatening stimuli. This project aimed to investigate the adaptations to stress that occur in the noradrenergic locus coeruleus (LC) and how these changes affect stress coping behavior. We began by investigating how adolescent restraint and predator odor stress affects coping when presented with a secondary noxious stimulus in the defensive shock probe burying task one week following stressor exposure, finding that stressed male rats demonstrate a more active coping response and stressed female rats demonstrate a more passive coping response, with active coping correlating with LC activation exclusively in male rats. After this, we began to investigate how viral changes in expression of the inhibitory δ-opioid receptor (DOR), which is normally downregulated in the LC following stress, could affect stress coping. From this, we found that knocking down LC DOR led to higher active escape behavior along with noticeable changes in electrophysiological measures of LC neurons, while overexpressing the DOR led to lower active escape behavior. Collectively, these findings reveal a role for LC DORs in exploratory or escape behaviors and provide a greater understanding of the involvement of the LC in stress coping.

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