# A novel role for Oligodendrocyte Progenitor Cells (OPC) in opiate addiction

> **NIH NIH K00** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $71,820

## Abstract

Project Summary / Abstract
Heroin addiction is a chronic brain disease that is characterized by compulsive drug intake despite the
presence of negative consequences. Heroin addictions have a lifelong vulnerability to relapse, in part due to
heightened motivation to seek the drug. Unfortunately, pharmacotherapies for heroin addiction remain limited
and largely ineffective. In order to identify novel therapeutic targets to aid in the prevention of relapse, the
molecular mechanism of behaviors leading to relapse, specifically motivation, must be better understood. It is
known that drugs of abuse induce plasticity in key regions of the mesolimbic dopamine system, including the
prefrontal cortex (PFC). Specifically, alterations within this region have been associated with the maladaptive
behaviors associated with addiction, including motivation for drug reinforcers, which can be assed using a
progressive ratio test in both the human condition and animal models of addiction. While many of the cellular
adaptions induced by heroin have predominately focused on the neuronal cells within the PFC, our preliminary
data, presented in Aim 1, has identified a dysregulation in glial cells, and specifically oligodendrocytes,
following heroin self-administration, an animal model of addiction. I have shown that a transcription factor key
in the regulation of oligodendrocyte progenitor cell (OPC) differentiation, Sox10, is upregulated in the PFC
following heroin self-administration via chromatin remodeler BRG1. Furthermore, I have identified Sox10 as a
critical mediator in a hallmark behavior associated with addiction, motivation to seek the drug. While these
novel studies have added to our understanding of the role of glial transcripts in the addicted state, the changes
that are occurring specifically in progenitor population, versus cells of the whole lineage, remain unknown.
Therefore, I am proposing to examine cellular changes in a specific subtype of OPCs, NG2+ cells, which have
distinct physiology properties from other glial cells. My central hypothesis in Aim 2 is that heroin induces
transcriptomic changes within the NG2+ cells in the PFC compared to saline controls. I will determine the
cell-type specific alterations in genes transcription in this subset of cells using genetic mouse models combined
with viral-mediated gene transfer to selectively purify RNA from NG2 cells using Translating Ribosomal Affinity
Purification (TRAP). The RNA will be analyzed for transcript changes using RNA-sequencing. Scientifically,
this proposal will establish a critical role for NG2 cells in the heroin-addicted state. While these studies are
underway, I will participate in a multifaceted Training Plan designed to develop the non-bench skills necessary
to reach my ultimate goals of becoming a tenured faculty in an academic setting. In addition, Aim 3 was
designed to aid in the identification of a well-funded postdoctoral mentor who continue to help me develop the
skills necess...

## Key facts

- **NIH application ID:** 9979987
- **Project number:** 5K00MH122356-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Jennifer Martin
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,820
- **Award type:** 5
- **Project period:** 2019-07-01 → 2020-07-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979987

## Citation

> US National Institutes of Health, RePORTER application 9979987, A novel role for Oligodendrocyte Progenitor Cells (OPC) in opiate addiction (5K00MH122356-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9979987. Licensed CC0.

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