# Understanding neuronal subtype-specific function of NAc in cocaine addiction

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $723,004

## Abstract

Understanding neuronal subtype-specific function of NAc 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 brain reward system play a central role in the
development of addictive disorders. However, the underlying 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. Accumulating evidence suggests that drug-induced molecular, cellular
and circuitry changes, especially those in the nucleus accumbens (NAc), play important roles in drug
addiction. However, due to the cellular heterogeneity of the mammalian brain, the cell type-specific
mechanism of addition is unknown.
 To overcome the cell heterogeneity issue and to advance our understanding of the cell subtype-
specific mechanisms of drug addiction, we propose to identify the neuronal subtypes in NAc involved
in addiction by comprehensively analyzing the transcriptional profiles of this brain region in a neuron
subtype-specific manner, using a clinically relevant intravenous cocaine self-administration (IVSA)
mouse model. Furthermore, cell type-specific profiling/manipulation approaches will be used to
understand the function and mechanism of specific neuron subtypes during addictive process. To
achieve this goal, we have the following specific aims:
1) Profile cell type-specific transcriptome of different neuron subtypes of NAc using a mouse model of
 cocaine IVSA;
2) The function and circuitry mechanisms of Tac2+ D1 MSN subtype in cocaine addiction;
3) Understand the epigenetic mechanism of the neuron subtype-specific functions in cocaine
addiction.
 Completion of the proposed study will not only advance our understanding on how different NAc
neuron subtypes contribute to drug addiction, but also reveal novel therapeutic targets for treating this
disorder.

## Key facts

- **NIH application ID:** 10381647
- **Project number:** 5R01DA050589-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Yi Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $723,004
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381647

## Citation

> US National Institutes of Health, RePORTER application 10381647, Understanding neuronal subtype-specific function of NAc in cocaine addiction (5R01DA050589-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10381647. Licensed CC0.

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