Date Approved

5-27-2026

Embargo Period

5-27-2026

Document Type

Dissertation

Degree Name

Ph.D. Neuroscience

Department

Neuroscience

College

Rowan-Virtua School of Translational Biomedical Engineering & Sciences

Advisor

Daniel Manvich, Ph.D.

Committee Member 1

Rachel Navarra, Ph.D.

Committee Member 2

Daniel Chandler, Ph.D.

Committee Member 3

Jessica Loweth, Ph.D.

Committee Member 4

Mathieu Wimmer, Ph.D.

Keywords

Addiction Neuroscience;Behavioral Neuroscience;Opioids;Pharmacology

Disciplines

Medical Sciences | Medicine and Health Sciences | Neurosciences

Abstract

Opioid Use Disorder (OUD) and opioid-associated overdoses continue to pose significant burden to US healthcare systems—both financially and in lives lost. It is imperative to identify risk factors which may predispose vulnerability to OUD development, which could aid in discovery of new therapeutic strategies for susceptible populations. This dissertation investigated the impacts of two such risk factors which modulate opioid-induced reward and behavioral effects: adolescent stress and the adulteration of illicit opioids by xylazine. In Chapter 2, we examined the effects of acute adolescent stress on oxycodone self-administration in rats, and the potential involvement of the locus coeruleus in these effects. Here we found that adolescent stress enhanced maintenance of oxycodone self-administration, however, we could not determine a role for the locus coeruleus in this phenomenon. Due to the rapidly emerging threat of α2 receptor agonist adulteration of the illicit drug supply, in Chapter 3, we investigated whether xylazine impacts the discriminative stimulus effects of fentanyl. We found that xylazine prolonged the duration of the discriminative stimulus effects of fentanyl and enhanced fentanyl-induced behavioral suppression. Furthermore, we found that dual opioid/α2 receptor antagonism reversed the discriminative stimulus and rate-suppressing effects of fentanyl-xylazine.

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