# Elucidating behavior and neural circuits underlying opioid addiction and dependence

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $161,358

## Abstract

Project Summary/Abstract
 Prescription opioid addiction is a significant problem characterized by compulsive drug seeking,
withdrawal and chronic relapse. Despite the growing impact of prescription opioids on public health, relatively
few pre-clinical studies have investigated the neurobiological mechanisms underlying self-administration of
oxycodone, a commonly prescribed medication. Neural circuits in the extended amygdala mediate emotional
behaviors, and dysregulation of these reward and stress systems is a hallmark of drug dependence and
withdrawal. Models of intravenous drug self-administration are a standard paradigm for investigating the
reinforcing effects of drugs, and I have developed a model of oxycodone self-administration under extended
access conditions (12 hours/day) that produces robust escalation of drug-seeking behavior and provides a
translationally relevant model of opioid abuse. We hypothesize that escalation of oxycodone abuse and
dependence are mediated by withdrawal-induced changes in neural signaling mechanisms, and that the
manipulation of these underlying neural systems will attenuate the promotion of drug-seeking behavior. We will
test this hypothesis using behavioral pharmacology, chemogenetics, and immunohistochemistry in a rat model
of oxycodone self-administration under extended access conditions.
 My research training will be supervised by my mentors, Drs. Michael Taffe, Thomas Kash and Candice
Contet, with additional support from Dr. Bryan Roth as consultant and Drs. Marisa Roberto, Kim Janda and
Michael Forster as advisors for my career development. We have designed a multidisciplinary project that
utilizes different experimental modalities that allow for behavioral, biochemical, and immunohistochemical
investigation of oxycodone addiction and dependence. Precise characterization of KOR activation will be
achieved through the use of the chemogenetic technology, designer receptors exclusively activated by
designer drugs (DREADDs). We will employ neural circuit manipulations, specifically the inhibitory Gi-coupled
kappa opioid receptor DREADD (KORD) in the central nucleus of the amygdala (CeA) GABAergic projection to
paraventricular nucleus of the hypothalamus (PVN) to understand the effect of opioid-induced
neuroadaptations mediating drug-seeking behavior. I will train in DREADD-based and immunohistochemical
techniques to complement my experience in behavioral opioid pharmacology. These skills will be acquired
during my K99 phase at The Scripps Research Institute and will be further implemented at my new institution
during the R00 phase. My mentor team will help me establish these techniques in my independent laboratory
to ensure experimental reproducibility. Collectively, this work will provide insight into the influence of kappa
opioid receptor signaling in amygdalar pathways mediating opioid addiction and dependence-induced
behavior.

## Key facts

- **NIH application ID:** 9997923
- **Project number:** 5K99DA047413-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jacques DucHuy Nguyen
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $161,358
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997923

## Citation

> US National Institutes of Health, RePORTER application 9997923, Elucidating behavior and neural circuits underlying opioid addiction and dependence (5K99DA047413-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997923. Licensed CC0.

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