# Glutamatergic adaptation to stress as a mechanism for anhedonia and treatment response with ketamine

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $58,580

## Abstract

PROJECT SUMMARY
 Anhedonia, defined as a reduced interest in or motivation for rewards, is a core symptom of depression
that has been linked to reduced treatment response and increased risk of suicide. A key risk factor for the
development of anhedonia is chronic stress, which has further been shown to impact function within the
mesolimbic dopamine (DA). DA is a key neurotransmitter for motivation; both clinical and preclinical studies
have shown that dopamine depletion reduces willingness to expend effort. To date, however, human studies
linking dysregulation of dopamine to stress-induced anhedonia are lacking. This is due in part to the challenges
associated with taking in vivo measurements of dopamine in humans. Dopamine activity is commonly
measured in human studies using positron emission tomography (PET) imaging. PET is a popular
neuroimaging technique used to provide measurements of dopamine activity. However, it is costly, invasive,
and necessitates exposure to radiation. These factors make it difficult to conduct large scale studies.
Neuromelanin magnetic resonance imaging (NM-MRI) is a relatively new non-invasive imaging technique used
to take proxy measurements of dopamine. NM-MRI works by imaging neuromelanin, a pigment that
accumulates in high concentrations in dopamine neurons, over the lifespan. Prior studies have shown that NM-
MRI signal is correlated with PET signal. In short, NM-MRI can provide proxy measurements of dopamine
without the same limitations posed by PET. In the current study, we will examine associations between NM-
MRI signal and behavioral and neural measures of motivational anhedonia. We will also explore the
relationship between NM-MRI signal and fMRI measures of corticostriatal circuit function. Lastly, we will
examine the relationship between NM-MRI signal and physiological and self-report measures of stress. By
completing this study, the PI will gain the opportunity to grow as an independent researcher and become a
more competitive post-doctoral candidate.

## Key facts

- **NIH application ID:** 11002828
- **Project number:** 3R01MH126083-03S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Michael Tilghman Treadway
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $58,580
- **Award type:** 3
- **Project period:** 2022-03-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11002828

## Citation

> US National Institutes of Health, RePORTER application 11002828, Glutamatergic adaptation to stress as a mechanism for anhedonia and treatment response with ketamine (3R01MH126083-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11002828. Licensed CC0.

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