# Transcriptional Mechanisms of Drug Addiction

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $1,683,245

## Abstract

PROJECT SUMMARY/ABSTRACT – OVERALL PPG
 Our Program Project Grant (PPG) exploits advances in transcriptional biology to fundamentally increase
our knowledge of the lasting abnormalities in brain that underlie stimulant and opioid addiction. We focus on
specific cell types in nucleus accumbens and dorsal striatum, key brain regions implicated in addiction. The
PPG is composed of four Projects and three Cores all at Mount Sinai. The PIs are leaders in their fields, with
an established history of effective collaboration, and use their complementary expertise to chart a multi-
disciplinary course in the proposed research. Project 1 (Eric Nestler) focuses on transcription factors induced
in brain reward regions by self-administered (SA) stimulants and opioids. Project 2 (Paul Kenny) characterizes
specific neuronal microRNAs, which control gene expression in these regions and drug SA behavior, and
which are regulated by microglia. Project 3 defines subpopulations of microglia in striatum—including a subset
that expresses the D1 dopamine receptor—that modulate neuronal transcription and behavioral responses to
drug exposure including SA. Project 4 (Yasmin Hurd) concentrates on the influence of genomic enhancer
regions, and their transcriptional and chromatin mediators, in governing molecular and behavioral adaptations
to drugs of abuse. All four projects validate findings from animals in human postmortem brain tissue, while
discoveries in humans are fed back to animal models to explicate the underlying mechanisms involved. The
PPG is supported by three Cores, an Administrative Core (Eric Nestler) to oversee and coordinate PPG
operations; an Animal Models Core (Paul Kenny, Richard O’Connor) to provide animal models of addiction and
other advanced tools (e.g., viral gene transfer, inducible mutant mice, opto- and chemogenetics, and fiber
photometry) to manipulate individual genes of interest in specific cell types of the targeted brain regions and
thereby provide causal evidence linking molecular-cellular plasticity to addiction-related phenomena; and a
Gene and Chromatin Analysis Core (Li Shen) to provide state-of-the-art methods and bioinformatics to
characterize genome-wide regulation of gene expression and chromatin modifications in addiction. This
pioneering investigation of transcriptional mechanisms of drug addiction is driving major advances in the field.

## Key facts

- **NIH application ID:** 10934806
- **Project number:** 2P01DA047233-06A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** ERIC J. NESTLER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,683,245
- **Award type:** 2
- **Project period:** 2019-02-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934806

## Citation

> US National Institutes of Health, RePORTER application 10934806, Transcriptional Mechanisms of Drug Addiction (2P01DA047233-06A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10934806. Licensed CC0.

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