# Glucocorticoid regulation of dopamine circuit function

> **NIH NIH F99** · NORTHWESTERN UNIVERSITY · 2022 · $42,965

## Abstract

PROJECT ABSTRACT
Stress precipitates and exacerbates numerous psychiatric disorders, including major depressive disorder
(MDD). Symptoms of MDD include deficits in reward processing, which affect how individuals engage with their
environment. Moreover, individuals with MDD exhibit higher levels of the ‘stress hormone’, cortisol (CORT;
corticosterone in rodents), in their plasma relative to healthy individuals. However, it remains unclear if
increased circulating plasma CORT contributes to symptoms of MDD, such as deficits in reward processing.
Dopaminergic signaling plays a key role in reward processing, thus elucidating the mechanisms by which
stress affects dopaminergic signaling is critical for understanding how stress impairs reward processing and
contributes to the symptomology of MDD. The long-term goal of this project is to elucidate the mechanism by
which the stress hormone, corticosterone (cortisol in humans), affects dopaminergic circuit function.
Preliminary data in Aim 1.1 suggest that elevated circulating plasma CORT impairs reward-seeking behaviors
by impairing dopamine homeostasis in the dorsomedial striatum via alteration of post-translational
modifications on the dopamine transporter, DAT. Given the role of the glucocorticoid receptor (GR; a receptor
for CORT) as a transcription factor, it’s possible that CORT-induced transcriptional changes in dopamine
neurons may be driving the effect of CORT on DAT function. In Aim 1.2, I will investigate how endogenous,
and elevated levels, of circulating CORT affect GR-induced gene expression in dopamine neurons. The results
of these studies may inform the search for novel therapeutic targets for the treatment of stress-induced
motivational deficits.
The training plan under this award integrates professional development courses in grantsmanship and
business management, with scientific training in gene editing and gene expression analysis. Northwestern
University is well-suited to facilitate excellent professional development for the applicant due to the
collaborative nature of its graduate schools in business and the life sciences. The applicant will conclude the
fellowship period with expert training in multiple levels of scientific analysis due to the range of technical
expertise between the sponsor and co-sponsor. Overall, training under this award will provide the applicant
with exceptional preparation for independence in the biomedical workforce and beyond.

## Key facts

- **NIH application ID:** 10610046
- **Project number:** 1F99NS130873-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ashley Holloway
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,965
- **Award type:** 1
- **Project period:** 2022-09-15 → 2023-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10610046

## Citation

> US National Institutes of Health, RePORTER application 10610046, Glucocorticoid regulation of dopamine circuit function (1F99NS130873-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10610046. Licensed CC0.

---

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