Date of Award

2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmacology

First Advisor

James Stafford

Second Advisor

Elizabeth Bonney

Abstract

Opioid Use Disorder is a growing problem in the United States. During the 2000s, approximately 75% of opioid use disorders were initiated through the misuse of prescription opioids, particularly among women. With a rise in opioid use disorder and overdoses across the nation, there has also been a dramatic rise in neonatal withdrawal syndrome (NOWS). Prenatal opioid exposure is known to have long term effects on children’s development, including effects on learning, social behavior, and deteriorating school performance. The majority of prenatal opioid exposure rodent models utilize injection for delivery of opioids to mothers during pregnancy. These studies trade translatability for controlled dosing prenatally. Opioid addiction is driven by the reward pathway in the brain, and to accurately model addiction in rodents, the rodents must engage in the act of drug administration by the same route of administration commonly used by humans.

This thesis explores the use of a volitional drug administration apparatus to model sustained, high levels of oxycodone and buprenorphine in a gelatin vehicle from pregestational day 14 through postnatal day 22. We found that female mice readily consumed physiologically relevant doses of oxycodone or buprenorphine when given in the home cage over the course of 7.5-10 hours. To model prenatal opioid exposure, we utilized three groups of mice with varying exposure to opioids. These groups were continuous oxycodone, buprenorphine treatment initiated on gestational day 12, and a control group that received continuous sugar gelatin. We compared early developmental milestones between the treatment groups as well as sociability in the offspring. Pups born to vehicle dams had significantly longer survival than those prenatally exposed to either opioid. There was a significant difference in weight gain over time by drug treatment. We also found there was no significant difference between groups in sociability measures, and that all groups preferred contact with the novel mouse over novel object. This study opens the door on further experiments utilizing our volitional drug administration apparatus. Future directions include the confirmation of physiologically relevant blood levels of the chosen opioid from oral consumption of the gelatin vehicle, and the exploration of exposure to other types of emerging illicit opioids, such as fentanyl, on offspring.

Language

en

Number of Pages

55 p.

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