# The Impact of Fetal Methadone Exposure on Alcohol-Related Behavior and Alcohol-Induced Changes in the Striatum

> **NIH NIH F30** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $44,006

## Abstract

PROJECT SUMMARY
As the prevalence of opioid use disorder in pregnant women has grown, the number of neonates exposed to
opioids in utero has risen sharply. Despite the gap in knowledge regarding the impact of opioids on fetal
development, opioid maintenance therapies, such as methadone, are the standard of care for pregnant women
with opioid use disorder. Prior studies have shown that animals exposed to opioids during gestation demonstrate
an enhanced reward phenotype to opioids and other abused drugs. Although alcohol represents the most likely
abused drug this growing population of infants with fetal opioid exposure will encounter and consume as they
mature, no studies to our knowledge have examined how fetal opioid exposure impacts alcohol drinking patterns
or alcohol-related neurobehavioral adaptations. Because problematic drinking and alcohol use disorder (AUD)
is associated with significant morbidity, mortality, and social and economic burden, it is imperative that we
examine if fetal opioid exposure puts individuals at risk for problematic drinking patterns or AUD. Furthermore,
few studies have investigated underlying neuroadaptations in brain regions important for reward related
behavior, such as the striatum, which may contribute to this enhanced alcohol reward phenotype in fetal opioid
exposed animals. To address these unexplored questions, our laboratory has developed a translational mouse
model that seeks to resemble human patterns of opioid exposure in a typical pregnant woman who is first
dependent on oxycodone prior to gestation, then enters a methadone maintenance therapy program, and
subsequently becomes pregnant while maintained on methadone. This translational model of fetal methadone
exposure (FME) produces rodent pups which exhibit clinical symptomology reminiscence of neonatal opioid
withdrawal syndrome when challenged with naloxone. Furthermore, these pups with FME display significantly
increased expression of whole-brain N2B-containing NMDA receptors. The central goal of the proposal is to use
this animal model of FME to explore (1) if FME alters alcohol-induced behavioral adaptations and voluntary
alcohol drinking patterns; and (2) if FME produces persistent neuroadaptations in the four major striatal
subregions which primes these regions to differentially respond to alcohol compared to control animals. Towards
this goal, Aim 1 will examine alcohol locomotor sensitization and alcohol intake, utilizing the binge-alcohol
drinking in the dark model in adolescent mice with prior FME. In Aim 2, whole cell patch clamp electrophysiology
recordings and quantitative western blotting will be used to characterize glutamate transmission and glutamate
receptor expression, respectively, in mice with FME following different stages of voluntary alcohol drinking. As a
result, it is expected that our results will help to determine if FME predisposes individuals to future problematic
alcohol drinking behavior which may aid in developing str...

## Key facts

- **NIH application ID:** 10065251
- **Project number:** 1F30AA028687-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Gregory Giovanni Grecco
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $44,006
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065251

## Citation

> US National Institutes of Health, RePORTER application 10065251, The Impact of Fetal Methadone Exposure on Alcohol-Related Behavior and Alcohol-Induced Changes in the Striatum (1F30AA028687-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065251. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*