# Neonatal Opioid Exposure and Withdrawal: Molecular and Behavioral Consequences

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $712,968

## Abstract

Project Summary
Opioid use among pregnant women is a growing public health concern in the United
States. Infants exposed to opioids in utero are at high risk of exhibiting Neonatal Opioid
Withdrawal Syndrome (NOWS), a combination of physical withdrawal symptoms including
high pitched crying, sleeplessness, irritability, gastrointestinal distress, and in the worst
cases, seizures. The complexity of this syndrome is amplified by a variety of clinical factors
such as duration of maternal opioid exposure, maternal polypharmacy, environment, and
genetics. The complexity of in utero opioid exposure and NOWS make it very difficult to
investigate underlying molecular mechanisms that could ultimately inform early diagnosis
and treatment. Therefore, we have developed a much needed mouse model of 3-
trimester opioid exposure and withdrawal. Based on preliminary evidence, we hypothesize
that microglia activation and immune mediators contribute to the severity of NOWS and
a common SNP in the -opioid receptor modulates these effects. Using morphine as a
prototypical opioid, we will exploit our model to test these hypotheses. First we will fully
characterize the role of the innate immune system in NOWS and determine if regulation
of neuroinflammation has therapeutic potential by pharmacological treatment with the anti-
inflammatory drug, ibudilast. Second, as recent clinical findings suggest that genomic
variation in the gene that encodes the -opioid receptor (Oprm1 A118G) may influence
NOWS severity, we will use our mouse line that contains the equivalent Oprm1 A118G
SNP to determine the impact of Oprm1 genetics on microglia activation and immune
mediators. Using our model of 3-trimester opioid exposure and withdrawal we will use
TRAP-Seq, a new technology for retrieving mRNAs within the ribosomal complex that are
actively being translated, in our case in cells expressing m-opioid receptors, to interrogate
the changing transcriptome following opioid exposure and withdrawal. This project is likely
to have a sustained and powerful impact on the field because we will address
mechanisms through which perinatal exposure to opiates results in NOWS, and how
genetics and immune response contribute.

## Key facts

- **NIH application ID:** 10131172
- **Project number:** 5R01DA047743-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Julie A Blendy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $712,968
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131172

## Citation

> US National Institutes of Health, RePORTER application 10131172, Neonatal Opioid Exposure and Withdrawal: Molecular and Behavioral Consequences (5R01DA047743-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131172. Licensed CC0.

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