# Dopamine neurotransmission in Gulf War Veteran's Illness

> **NIH VA I01** · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · 2021 · —

## Abstract

ABSTRACT
 Because of uncertain pathophysiology, it is a challenge to effectively treat patients with Gulf War
Veterans’ Illness (GWVI). For formulation of an effective therapeutic strategy it is important to explore its
pathophysiology and understand neurocognitive bases of the symptoms. Most investigators believe that the
illness is caused by exposure to pesticides and other chemical agents. Interestingly, many of these agents
(e.g. permethrin and sarin) deplete dopamine in laboratory animals. These findings are important because
neuroimaging studies have found attenuated dopaminergic activity and reduced functioning neural mass in
the basal ganglia of GWVI patients. Further, most of the common symptoms of GWVI are elicited by
depleted dopamine. Thus, a vast majority of patients complain of clinical depression, memory loss, and
unexplained pain. Depletion of dopamine is believed to cause depressive symptoms by disrupting dopamine
dependent processing of the brain reward system. Similarly, a number of clinical and cognitive experiments
have reported memory deficits and spontaneous unexplained pain after dopamine is depleted. Therefore,
both of these symptoms along with clinical depression, are common clinical symptoms in Parkinson’s
disease. Thus, converging evidence from etiological, neuroimaging, cognitive, and clinical data suggests
that dopamine neurotransmission is depleted in GWVI. We hypothesize that dysregulated dopamine
neurotransmission is an important deficit in GWVI. In this study, we propose to examine validity of this
hypothesis using a newly developed neurotransmitter imaging technique, called the single scan dynamic
molecular imaging technique or SDMIT. In the proposed experiments tonic (resting) and phasic (task-
induced) release of dopamine will be detected, mapped and measured in GWVI and healthy control
volunteers. For measurement of the tonic release, binding potentials of dopamine receptor ligands (11C-
raclopride and 18F-fallypride) will be estimated in the striatal and extrastriatal areas of the brain. The phasic
release will be measured in GWVI and healthy control veterans during performance of tasks that elicit
reward (a proxy for clinical depression), memory, and nociceptive processing. Comparison of the data
acquired in the two groups will indicate whether tonic or phasic release of dopamine is dysregulated in
GWVI. In all of these experiments we propose to use the ligand 11C-raclopride to study dopamine release
inside the striatum and a high affinity ligand 18F-fallypride to study dopamine outside the striatum. We have
to use separate ligands for the striatal and extrastriatal studies because receptor kinetic properties of none
of the dopamine ligands allow detection of binding and displacement in the whole brain. Further, we
propose to correlate deficits in task performance with the amount of dopamine release, to understand
whether dysregulated dopamine neurotransmission is responsible for the symptoms of GWVI. Thus,...

## Key facts

- **NIH application ID:** 10260710
- **Project number:** 1I01CX002099-01A1
- **Recipient organization:** SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
- **Principal Investigator:** RAJENDRA D BADGAIYAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-04-01 → 2021-11-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260710

## Citation

> US National Institutes of Health, RePORTER application 10260710, Dopamine neurotransmission in Gulf War Veteran's Illness (1I01CX002099-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10260710. Licensed CC0.

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