Date Approved

4-11-2025

Embargo Period

4-11-2025

Document Type

Dissertation

Degree Name

Ph.D. Neuroscience

Department

Cell Biology and Neuroscience

College

Rowan-Virtua School of Translational Biomedical Engineering & Sciences

Advisor

Jessica Loweth, Ph.D.

Committee Member 1

Elizabeth West-Niedringhaus, Ph.D.

Committee Member 2

Daniel Manvich, Ph.D.

Committee Member 3

Benjamin Rood, Ph.D.

Committee Member 4

Jacqueline Barker, Ph.D.

Keywords

Drug Seeking;Estrous Cycle;Incubation;Nucleus Accumbens;Oxycodone;Sex Differences

Disciplines

Medical Sciences | Medicine and Health Sciences | Neurosciences

Abstract

The overprescription and misuse of opioids like oxycodone has played a significant role in the ongoing opioid crisis. While effective painkillers, drugs like oxycodone are also reinforcing and often misused. While sex and ovarian hormones can impact the analgesic effects of these drugs, the impact of these factors on oxycodone reinforcement are not fully understood. This relationship between ovarian hormones and opioid reward is further complicated by the fact that opioid use can disrupt ovarian hormone levels and produce reproductive cycle irregularities. Using a rat model of drug craving and relapse vulnerability, we found that chronic oxycodone exposure produced reproductive (estrous) cycle dysregulation in the majority of animals (~60%) during both oxycodone self-administration and/or the first month of abstinence. During periods of normal cyclicity, we observed estrous cycle-dependent changes in both oxycodone intake and craving that differs from that found with other drugs like psychostimulants. We also observed estrous cycle-dependent changes in opioid receptor expression in the nucleus accumbens, a region that plays a critical role in drug seeking behavior. Together the studies in this thesis highlight the importance of ovarian hormones on oxycodone reinforcement and identify estrous cycle-dependent changes in the accumbens opioid receptor system that may contribute to these effects.

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