# Bidirectional Comorbidity Between Fear Sensitization and Opioid Reward

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $170,015

## Abstract

ABSTRACT
People suffering from anxiety disorders such as post-traumatic stress disorder (PTSD) very often use and
abuse reinforcing drugs such as opioids. Although the comorbidity of PTSD and substance abuse is
exceedingly high, little is known about the neurobiological mechanisms that result in this comorbidity. By
leveraging the Fanselow laboratory's development of a preclinical model of PTSD with the expertise within the
Center for Study of Opioid Receptors and Drugs of Abuse (CSORDA) we plan to attack this question. Based
on findings with our model we hypothesize that, during a single traumatic event, stress hormones
(corticosterone/cortisol) and neuromodulators (acetylcholine) act in concert on amygdala neurons resulting in
changes in neural plasticity within this brain structure. These changes result in the altered fear responses that
characterize several aspects of PTSD. The amygdala also contains neurons that participate in the rewarding
property of drugs and we hypothesize that trauma causes similar changes in those neurons and this leads to
increased drug reward learning. Therefore, in Aim 1 of this proposal we will determine if manipulations that
mitigate the potentiation of fear learning caused by trauma also mitigate alterations in drug responsivity
following trauma. Aim 2 seeks to identify a set of amygdala neurons that are activated by BOTH trauma and
drug exposure and using optogenetics tests if activity in these neurons is necessary for comorbidity. We will
also assess how stress and drug experience alter gene expression patterns in the amygdala. While most of the
focus on drug use/anxiety disorder comorbidity has focused on stress as a causal factor in altered drug taking,
we have obtained preliminary data that the converse is also true. A history of drug use and withdrawal
increases the impact that a future stressor has on fear processes. Aim 3 investigates potential mechanisms for
the ability of drug exposure to adversely impact fear behavior. We will determine if mu-opioid or kappa-opioid
receptors in the amygdala are necessary for morphine's effects on future stress reactivity. We will also use
resting state fMRI, with an amygdala seed, to determine the overlap in the modifications of whole brain
connectivity caused by drug exposure and by stress.

## Key facts

- **NIH application ID:** 9964749
- **Project number:** 5P50DA005010-34
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Michael S Fanselow
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $170,015
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964749

## Citation

> US National Institutes of Health, RePORTER application 9964749, Bidirectional Comorbidity Between Fear Sensitization and Opioid Reward (5P50DA005010-34). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9964749. Licensed CC0.

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