# The DNA methylation code governing the ensemble representation of morphine-context association

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $211,368

## Abstract

Abstract
Morphine is a widely-prescribed and potent opioid analgesic, but in recent years its non-medical use has
been on the rise and has contributed to the increased incidence of opioid use disorder. Repeated exposure
to morphine and other drugs of abuse leads to lasting learned associations between the rewarding
properties of the drug and the environment of administration. Therefore even in abstinence, re-exposure to
the context is a risk factor for relapse, increasing withdrawal symptoms and drug cravings. While the
neural circuits mediating drug-context associations and drug seeking behavior have been studied heavily,
the specific underlying mechanisms of these associations remain poorly understood. In the proposed
studies, we aim to evaluate the hypothesis that epigenetic alterations in the methylation of genes related to
neuronal connectivity and excitability during repeated morphine-context pairings provide a mechanism for
the stable recruitment of a small, specific population of neurons in the ventral hippocampus to the
‘engram” storing the memory of morphine-context associations. Switching the methylation status of these
genes alters gene expression, which leads to increased excitability and connectivity with pre- and
postsynaptic circuit cortical and limbic partners to enhance the morphine-context association and create a
lasting memory. By characterizing the changes in methylation in the recruited hippocampal neuronal
ensemble and evaluating the consequent effects on neuronal function and circuit plasticity, our
experiments may provide a new framework for the study of the mechanisms of opioid addiction and
contribute to more effective treatments of substance use disorder.

## Key facts

- **NIH application ID:** 9906873
- **Project number:** 5R21DA048635-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Kristen Elizabeth Pleil
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,368
- **Award type:** 5
- **Project period:** 2019-04-15 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906873

## Citation

> US National Institutes of Health, RePORTER application 9906873, The DNA methylation code governing the ensemble representation of morphine-context association (5R21DA048635-02). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9906873. Licensed CC0.

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