# Effects of Early Life Adversity on Opioid Addiction Vulnerability

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $40,672

## Abstract

Project Summary
Over the past twenty years, the United States has experienced a growing epidemic of opioid use disorder
accompanied by high rates of opioid-related mortality. Effective strategies to combat this crisis are urgently
needed, and identifying at-risk individuals before they become addicted will be critical for fighting this growing
epidemic. Although genetics play a role in addiction vulnerability, they alone cannot account for the dramatic rise
in opioid addiction incidence in recent years. Therefore, successful prevention strategies must also consider
environmental risk factors. For example, in humans, early-life adversity (ELA), such as low socioeconomic status,
trauma, or chaotic environment, is associated with life-long affective problems that indicate dysfunction of the
brain’s reward circuitry, including risk-taking behaviors and drug use. However, the neurobiological mechanisms
by which this occurs are unknown. My project will examine effects of ELA on drug-seeking behavior and reward
circuit function in rats, in pursuit of a mechanistic understanding that will inform novel translational intervention
or prevention strategies for opioid addiction. To this end, I will implement a powerful, naturalistic model of ELA
in rats. In this model, poverty is simulated by providing limited bedding and nesting materials to a postpartum
dam. This provokes chaotic patterns of maternal care that are analogous to humans experiencing ELA, and the
resulting chronic stress induces profound changes in reward circuits. To understand the behavioral implications
of these disrupted circuits, I will use established methods for modeling opioid addiction including self-
administration, extinction resistance, and reinstatement, as well as a recently-developed, translationally-relevant
behavioral economic model of opioid seeking that can also be used to quantify addiction severity in humans.
Building upon my recently-published findings that ELA-reared female rats are remarkably vulnerable to
developing opioid addiction-like behaviors, I will determine how ELA interacts with biologic sex to alter
vulnerability to opioid addiction in a potentially sex-specific manner. To define the neurobiological mechanisms
that underlie ELA-induced opioid vulnerability, I will test whether ELA alters heroin-induced activity within the
nucleus accumbens (NAc), and whether restoring normal activity in this region reverses augmented opioid-
seeking, thereby identifying a causal mechanism by which ELA shapes reward circuity to increase opioid
addiction vulnerability. These studies represent a unique opportunity to understand the role of developmental
risk factors in opioid addiction and will elucidate the neurobiological mechanisms that underlie these
vulnerabilities.

## Key facts

- **NIH application ID:** 10316158
- **Project number:** 5F30DA051137-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Sophia Levis
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,672
- **Award type:** 5
- **Project period:** 2020-07-09 → 2024-07-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316158

## Citation

> US National Institutes of Health, RePORTER application 10316158, Effects of Early Life Adversity on Opioid Addiction Vulnerability (5F30DA051137-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10316158. Licensed CC0.

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