# Prenatal oxycodone exposure: developmental effects on microglia and addiction-like behavior in rats

> **NIH NIH R21** · MCLEAN HOSPITAL · 2020 · $196,985

## Abstract

One devastating consequence of the current opioid epidemic is that opioid abuse and dependence among
pregnant women in the U.S. has more than doubled in the last 20 years, with the misuse of prescription opioids
comprising the largest percentage of such cases. This has resulted in an average of one infant born with neonatal
abstinence syndrome (NAS) every 25 minutes. Health care workers are struggling to handle the acute crisis of
NAS as well as the long-term health consequences for these infants. Not surprisingly, basic research on the
neurobiological effects of prenatal opioid exposure on brain development and motivated behavior is sorely
lacking. A PubMed search of “prenatal opioid exposure” in non-humans reported 408 publications since 1976,
with only 100 in the last 10 years. Our proposal explores the novel idea that prenatal exposure to oxycodone,
one of the most commonly abused prescription opioids, disrupts normal development of the mesocorticolimbic
dopamine reward system through aberrant microglia activation and function. Co-I Dr. Bilbo has recently
demonstrated in rats that during early adolescence, microglia in the nucleus accumbens (NAc), a brain region
necessary for reward and aversion, regulate dopamine D1 receptor (D1r) expression through coordinated
phagocytosis. This process is sex-dependent, as it occurs selectively in males. Her group has also shown that
adolescent morphine activates microglia and disrupts the normal process of microglia-mediated D1r engulfment,
raising the possibility that in utero exposure to opioids could derail the actions of microglia during development,
resulting in pathophysiologies in motivated behavior throughout the lifespan. PI Dr. Chartoff has recently
demonstrated that both male and female rats learn to self-administer the commonly abused prescription opioid,
oxycodone and show similar drug pharmacokinetics and dose response functions. Her group has also shown
that morphine withdrawal in adult rats results in dysregulated NAc D1r signaling and increased self-
administration of oxycodone. Taken together, this R21 proposal leverages the novel findings and unique skill
sets of the Chartoff and Bilbo labs to test the hypothesis that prenatal oxycodone exposure has both short- and
long-term effects on offspring through disruption of microglia development, microglia-mediated phagocytic
pruning of D1rs in the NAc, and increased sensitivity to reward-related effects of opioids. We will address this
hypothesis in two aims, both of which will use a clinically-relevant model of prenatal opioid exposure in which
female rats self-administer oxycodone before and throughout pregnancy. We will examine the effects of prenatal
oxycodone exposure on microglia structure/function and on microglial elimination of NAc D1rs in the NAc at early
postnatal and later (adolescent) stages (Aim 1) and on sensitivity to oxycodone-induced conditioned place
preferences in adolescence (Aim 2). These studies are designed to 1) expan...

## Key facts

- **NIH application ID:** 10025577
- **Project number:** 5R21DA048399-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** ELENA H CHARTOFF
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,985
- **Award type:** 5
- **Project period:** 2019-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025577

## Citation

> US National Institutes of Health, RePORTER application 10025577, Prenatal oxycodone exposure: developmental effects on microglia and addiction-like behavior in rats (5R21DA048399-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10025577. Licensed CC0.

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