# A novel model of oxycodone seeking that considers sex and stress susceptibility.

> **NIH NIH R03** · UNIVERSITY OF FLORIDA · 2020 · $76,250

## Abstract

ABSTRACT
Post-traumatic stress disorder (PTSD) is a debilitating disorder that develops in a subpopulation (~20-30%) of
people exposed to a traumatic event. PTSD is highly comorbid with substance use disorder (SUD), with alcohol,
stimulants and opioids being the most frequently abused drugs. Despite the prevalence of PTSD+SUD
comorbidity, animal models of such comorbidity are lacking and are sorely needed to screen potential treatments.
Here we will utilize our novel animal model of PTSD+SUD that captures several key features of PTSD+SUD
comorbidity: 1) PTSD typically arises from a single trauma, 2) not all trauma-exposed individuals develop PTSD,
3) post-trauma anxiety symptoms are long-lasting, and 4) increased drug-craving and resistance to traditional
interventions that reduce relapse in SUD. This model relies on exposing rodents to an ethologically-relevant
“trauma” - predator scent stress (PSS). We have successfully combined the PSS model of PTSD with the
extended access to cocaine self-administration to study PTSD+cocaine use disorder (CUD) in animals. The
present application proposes to adapt this animal model to study the interaction between opioid use disorder
(OUD) and PTSD. Our overall hypothesis is that, as we demonstrated for cocaine, stress-Susceptible rats will
display greater oxycodone seeking, a possible indication of similar neurobiological underpinnings of both cocaine
and opioid seeking in stress susceptible rats. We will assess opioid seeking using two models. Aim 1 will utilize
demand curve analyses (increasing the “cost” to obtain intravenous oxycodone infusions over days) to calculate
the essential demand for oxycodone and use regression models to assess the relationship between anxiety and
oxycodone demand. This work will be done in males and females, and thus, will be the first work to assess sex
differences in demand for oxycodone. We have found that stress-susceptibility results in increased cue-primed
reinstatement of cocaine-seeking and impaired instrumental extinction of the response made to obtain cocaine.
Aim 2 will assess if the same is true for oxycodone seeking, which would imply a common circuit or circuits
mediating enhanced stress susceptibility and drug-seeking and potentially lead to pharmacotherapies for
individuals with both OUD and CUD. Our rationale is that rat models that more closely model comorbidities
accompanying human substance use should more accurately reproduce the underlying neuroadaptations
present in humans, and should thus serve as better platforms for therapeutic discovery. As such, our central,
unified hypothesis is that susceptibility to stress remodels circuits involved in drug seeking in a similar manner
for cocaine and opioids. Future research proposals would interrogate neurobiological substrates and circuit(s)
involved in differential oxycodone seeking. For example, we have found that mGlu5 expression in the amygdala
and prefrontal cortex is increased in Resilient rats relative to...

## Key facts

- **NIH application ID:** 10057442
- **Project number:** 1R03DA050118-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Marek Schwendt
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,250
- **Award type:** 1
- **Project period:** 2020-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057442

## Citation

> US National Institutes of Health, RePORTER application 10057442, A novel model of oxycodone seeking that considers sex and stress susceptibility. (1R03DA050118-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10057442. Licensed CC0.

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