Author ORCID Identifier

https://orcid.org/0009-0003-2769-6773

Date of Award

5-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Anne Murphy

Second Advisor

Aaron Roseberry

Third Advisor

H. Elliott Albers

Fourth Advisor

Jesse Schank

Abstract

Every fifteen minutes, a baby is born in the U.S. experiencing neonatal opioid withdrawal syndrome. Clinical studies have established intrauterine exposure to drugs of abuse as a risk factor for adverse health outcomes in adolescence, including future drug use and depression. Although substantial evidence supports shared neural mechanisms underlying opioid and alcohol reward, there is limited data on the risks of alcohol use later in life for infants exposed to opioids. Additionally, ongoing research on the long-term consequences of perinatal opioid exposure (POE) has been limited to analyses of school performance and early life sociability. Our laboratory has developed a clinically relevant model for morphine exposure spanning pre-conception to the first postnatal week. Using this model, we report that perinatal opioid exposure increases alcohol consumption in female rats under noncontingent conditions, and inversely, reduces alcohol consumption in both sexes during operant conditioning sessions. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to drugs of abuse. Parallel studies examined the impact of perinatal morphine exposure on central expression of µ opioid receptors (MOR) at postnatal and adolescent ages. We report age and region-dependent changes in MOR within the nucleus accumbens and medial habenula, regions previously shown to play a significant role in reward/aversion circuitry. In extending our assessment of POE-induced changes in natural reward behaviors, we find reduced sucrose preference during adolescence. Juvenile and adult POE rats also spend less time socially interacting with familiar conspecifics. Changes in adult social behaviors were linked to increased nondopaminergic mesolimbic reward brain activity. We suggest that changes in reward outcomes may be linked to comparatively fragmented and unpredictable maternal behavior in opioid-dependent dams that disrupts pup development.

DOI

https://doi.org/10.57709/38141249

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