# Making and breaking opioid memories to prevent relapse

> **NIH NIH DP1** · VANDERBILT UNIVERSITY · 2020 · $474,000

## Abstract

Project Summary
Repeated drug exposure produces widespread cellular alterations that can manifest in maladaptive behaviors
and addiction. These behavioral alterations can be debilitating, and the pathology of addiction is often a life-long
affliction. Indeed, even after years of abstinence, relapse can be precipitated by exposure to drug-associated
cues. This is a ubiquitous property of drug addiction, and is present across drug class, yet we lack a clear
understanding of how these changes can be so long lasting. Dysregulation of many classes of proteins have
been implicated in cue-evoked relapse, yet the propensity to relapse persists well past the half-life of these
proteins, suggesting that upstream epigenetic changes are permissive to the transcriptional landscape that
produces these behavioral aberrations. Understanding the epigenetic alterations that ultimately produce these
cellular changes will great expand the number of targets available for potential therapeutic interventions. To
approach understanding the epigenetic mechanisms that underlie cue-induced relapse, we must identify the
cells that are activated to drive seeking behavior. Our preliminary data show that in any given brain region, only
a small percentage of cells are activated to a given stimulus – this group of activated neurons is termed a neural
ensemble. Thus, the next frontier of understanding the brain will be defining exactly which cells are activated,
when they are activated, and why. Here we combine techniques that allow us to record, manipulate, and
sequence neural ensembles during opioid self-administration and subsequent cue-triggered drug seeking to
determine how transcriptional activity within each neuronal population dictates which cells are activated. By
combining in vivo cellular resolution calcium imaging during cue-induced seeking followed by single cell
sequencing - in the same animals - we will define the transcriptional networks that control the neural activity
patterns that drive drug seeking. Next, using epigenetic approaches and CRISPR/dCas9 fusion constructs, we
will define and manipulate the epigenetic landscape at activity-responsive genes selectively in neurons that are
activated by drug-associated cues. This proposal will allow us to define the precise neural ensembles that guide
drug seeking and how transcriptional networks within these neurons control the neural activity profiles that guide
behavior. By defining these mechanisms, this award will allow research that pushes the boundaries of how we
approach understanding information encoding in the brain and expand our understanding of how we can
manipulate these processes to reduce relapse across drug classes.

## Key facts

- **NIH application ID:** 9964751
- **Project number:** 5DP1DA048931-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Erin Calipari
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,000
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964751

## Citation

> US National Institutes of Health, RePORTER application 9964751, Making and breaking opioid memories to prevent relapse (5DP1DA048931-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9964751. Licensed CC0.

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