# Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury

> **NIH NIH R01** · WEST VIRGINIA UNIVERSITY · 2020 · $216,340

## Abstract

Project Summary/Abstract
More than 2.8 million traumatic brain injuries (TBIs) occur annually, making this one of the most pressing
challenges facing the medical community. Survivors of TBI often experience chronic psychiatric symptoms
such as increased risky decision-making and impulsivity, yet there are no treatments specific to this large
population. These deficits affect individuals across all aspects of everyday life, often leading to reduced quality
of life for caregivers or those surrounding the person. A potential major contributor to this enduring dysfunction
is reduced dopamine neurotransmission, which mediates many core motivated behaviors in humans and
animals. Because of reductions in dopamine, these changes may alter the efficacy of rehabilitative efforts and
therapeutic drugs, making patients with TBI a special population in this regard. Thus, the goal of this project is
to investigate potential treatments for psychiatric-like deficits arising from chronic TBI, focusing on modulation
of dopamine systems, with the hypothesis that augmentation of dopamine will improve function. This will be
investigated across three aims, each with different treatment modalities, using a rat model of TBI. Proposed
studies will use an analog of the Iowa Gambling Task, known as the Rodent Gambling Task, to concurrently
assess risky decision-making and impulsivity after TBI. Aim 1 will investigate changes in sensitivity to
environmental contingencies to understand shifts in efficacy of rehabilitative training in humans. A series of
experiments will determine whether cueing of outcomes, a known means of stimulating dopamine responses,
can rescue decision-making ability. Aim 2 will test the efficacy of multiple therapeutic drugs. It will compare
how effective receptor-specific drugs are compared with general dopaminergic agents and what specific
changes occur to brain levels of dopamine-related proteins in the chronic injury period. Aim 3 will evaluate the
efficacy and mechanism of transcranial direct-current stimulation (tDCS) as a form of neural modulation. Prior
research has suggested that tDCS increases dopamine levels, but parameters have not been explored for
brain-injured subjects. To verify that dopamine is driving beneficial effects of tDCS, chemogenetic inhibition of
dopamine cells will be performed in the frontal cortex. These studies will advance fundamental understanding
of mechanisms of dysfunction after TBI, identify the efficacy of three different therapeutic modalities, and
determine the degree to which dopamine represents a relevant clinical target for chronic dysfunction after
injury.

## Key facts

- **NIH application ID:** 9928511
- **Project number:** 5R01NS110905-02
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Cole Vonder Haar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $216,340
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928511

## Citation

> US National Institutes of Health, RePORTER application 9928511, Dopamine modulation for the treatment of chronic dysfunction due to traumatic brain injury (5R01NS110905-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928511. Licensed CC0.

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