# Probing the contribution of stress-responsive neurons in the basolateral amygdala to stress enhanced opioid learning

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $40,532

## Abstract

Project Summary/Abstract
Post-traumatic stress disorder (PTSD) and opioid use disorder (OUD) are highly comorbid, resulting in worse
symptom severity and treatment outcomes than either disorder alone. Individuals with OUD appear to be
particularly susceptible to PTSD. Studying each disorder in isolation fails to capture the complexity of the
interrelationships between PTSD and OUD. While prior trauma tends to occur before the development of
substance use disorders, little is known about the causal mechanism of this relationship. Both PTSD and OUD
can be conceptualized as learning disorders, in which opioid- or fear-associated cues gain a strong control over
behaviors. In order to advance our understanding of PTSD and OUD comorbidities, the goal of this proposed
research is to shed light on the stress-induced neuroadaptations that may promote vulnerability for opioid
learning and reward.
 The Fanselow laboratory has developed a stressor model that recapitulates some of the symptomology
of PTSD. In this stressor model, severe stress sensitizes future fear learning. I demonstrated that severe stress
additionally enhances future opioid-context learning. Both this stressor model and opioid-context learning are
dependent on basolateral amygdala (BLA) activity. Stress enhances the excitability and neural plasticity in the
BLA, leading to the intriguing possibility that severe stress fundamentally changes learning processes in the
BLA, making individuals more susceptible to opioid reward learning. Using a novel activity-dependent labeling
technique in a rat model, the first aim of this proposal will examine whether there is significant overlap in neurons
activated by severe stress and morphine-context pairing. Such findings would provide evidence that neurons
responsive to severe stress directly engage in future opioid-reward cue learning. The second aim in this proposal
will examine if stress-responsive neurons are necessary for stress enhanced opioid learning. This work will
promote an interdisciplinary training experience involving a combination of sophisticated behavioral approaches
paired with in vivo chemogenetic, in vivo activity-dependent labeling, and ex vivo analysis techniques that will
ultimately broaden our understanding of how traumatic stress can lead to development of OUD. These
experiments will be conducted at UCLA, an excellent training environment that prioritizes productivity,
mentorship, and collaboration, ensuring the success of the project.

## Key facts

- **NIH application ID:** 10315181
- **Project number:** 1F31DA054792-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jamie Elizabeth Mondello
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,532
- **Award type:** 1
- **Project period:** 2021-09-13 → 2024-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315181

## Citation

> US National Institutes of Health, RePORTER application 10315181, Probing the contribution of stress-responsive neurons in the basolateral amygdala to stress enhanced opioid learning (1F31DA054792-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10315181. Licensed CC0.

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