# Peripheral nerve stimulation for control of the mesolimbic dopamine system

> **NIH NIH R21** · UNIVERSITY OF TEXAS DALLAS · 2022 · $195,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The vagus nerve is an important carrier of appetitive and nutritive information from the gut and other visceral
organs to the central nervous system (CNS). New studies are revealing surprising and striking differences
between left and right vagal connectivity within the CNS. In particular, it was recently shown that activation of
ascending gut-brain projections through the right, but not the left, vagus nerve may activate classical
dopaminergic “reward” circuits within the central nervous system. These recent findings raise the intriguing
possibility that electrical vagus nerve stimulation (VNS) delivered to the right cervical nerve, rather than the
traditionally-targeted left cervical nerve, could be used to modulate activity within these reward networks,
providing novel strategies for the treatment of neurological disorders. However, both left and right vagal fibers
branch extensively in the periphery and carry information from the gut as well as liver, pancreas, and other
organs capable of conveying potentially rewarding nutritive or metabolic information. Additional research is thus
needed to fully understand the functional and clinical relevance of lateralized vagal signaling.
Understanding whether and how lateralized vagal stimulation differentially activates reward networks is crucial
for further clinical development of this therapeutic technology. Left cervical VNS (l-VNS) is currently FDA
approved for the treatment of epilepsy and major depressive disorders, and is rapidly emerging as a treatment
to promote weight loss, extinction of drug seeking, and motor rehabilitation after neural injuries. Importantly, the
effectiveness of VNS over this expanded set of therapeutic indications depends on optimal activation of the
dopaminergic pathways known to support reward-related reinforcement of behavior. Thus, targeted modulation
of these pathways could provide additional mechanisms to induce therapeutic neuroplasticity. Delivery of VNS
to the right cervical nerve may therefore offer additional benefits compared to traditional l-VNS for the treatment
of e.g., obesity, addiction, mood, or motor disorders.
In the current proposal, we aim to determine the functional relevance and therapeutic potential of the differential
recruitment of midbrain dopaminergic networks by left versus right VNS. The proposed studies critically test our
hypothesis that right-VNS and left-VNS differentially engage midbrain DA networks, resulting in lateralized VNS
effects on motor and appetitive behaviors. These studies will provide fundamental insights into neurobiological
mechanisms underlying lateralized vagal signaling, and critically inform the development and optimization of
novel VNS strategies for therapeutic modulation of the DA system.

## Key facts

- **NIH application ID:** 10527834
- **Project number:** 1R21DA055166-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** CATHERINE A THORN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527834

## Citation

> US National Institutes of Health, RePORTER application 10527834, Peripheral nerve stimulation for control of the mesolimbic dopamine system (1R21DA055166-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10527834. Licensed CC0.

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