# Role of DNA Methylation in Cocaine Addiction

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $566,366

## Abstract

Role of DNA methylation in cocaine addiction
Abstract
 Drug addiction is a chronic, relapsing brain disorder characterized by compulsive drug seeking and use
despite harmful consequences. It is an urgent social and health problem contributing to more than 90,000 deaths
and incurs a yearly cost of over $700 billion in the United States (see NIDA website). It is believed that long-term
maladaptive changes in the mesolimbic dopamine reward system play a central role in the development of
addictive disorders. However, the underlying molecular mechanism remains largely unknown.
 The long-lasting effect of drugs on animal behavior and the risk of relapse in human addicts indicate that
some stable changes in the brain reward system induced by drugs of abuse mediate these long-term behavioral
adaptions. Accordingly, accumulating evidence suggests that drug-induced epigenetic changes, particularly
DNA methylation and histone modifications changes, play important roles in drug addiction. However, due to
technical difficulties in dealing with the cellular heterogeneity of the mammalian brain, most of the molecular
studies performed so far used mixed cell populations, making interpretation of the available data difficult.
Consequently, limited progress has been made in understanding the molecular basis of drug addiction.
 To overcome the issue of cell heterogeneity and to advance our understanding of the epigenetic
mechanisms underlying drug addiction, we propose to comprehensively analyze the role of DNA methylation in
drug addiction in a neuron subtype- and projection-specific manner using a clinically relevant intravenous
cocaine self-administration (IVSA) model. Specifically, we seek to elucidate how DNA methylation in ventral
tegmental area (VTA) dopaminergic neurons regulates cocaine reinforcement. To achieve this goal, we have
established the following specific aims:
1) Profile transcriptome and methylome of VTA dopaminergic (DA) neurons using a mouse cocaine IVSA model;
2) Functional analysis of key genes regulating DNA methylation in VTA DA neurons;
3) Understand the role of DNA methylation in cocaine reinforcement in projection-specific VTA DA neurons.
 Completion of the proposed study will not only advance our understanding of how DNA methylation
contributes to drug addiction, but also reveal novel therapeutic targets for treating this disorder. Importantly, our
study provides a novel, broadly applicable strategy for understanding epigenetic regulation in a neuron subtype-
and projection-specific manner.

## Key facts

- **NIH application ID:** 9878092
- **Project number:** 5R01DA042283-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Yi Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $566,366
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878092

## Citation

> US National Institutes of Health, RePORTER application 9878092, Role of DNA Methylation in Cocaine Addiction (5R01DA042283-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878092. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*