# Neural mechanisms of nausea, vomiting, and energy balance dysregulation in animal models

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $361,901

## Abstract

Project Summary
 Nausea, vomiting, and anorexia are common side effects of enumerable therapeutic drugs, diseases, and
disease treatments. An extreme example of this is emetogenic chemotherapy (EC)-induced nausea and
vomiting (CINV) and energy balance dysregulation, which devastate quality of life and obviate treatment
adherence. Strikingly, complete control of CINV and energy balance dysregulation has not been achieved,
despite the fact that an estimated 650,000 cancer patients undergo chemotherapy each year. The neural
circuits that are engaged by chemotherapy to produce CINV and energy balance dysregulation remain elusive.
Recent data identify a circuit of EC-activated nucleus tractus solitarius (NTS) neurons that project to the lateral
parabrachial nucleus (lPBN), and EC-activated lPBN neurons that project to the central nucleus of the
amygdala (CeA) in the rat. Further results indicate that CeA glutamate receptor signaling, potentially via the
lPBN→CeA projection, is necessary for the full expression of EC-induced pica (a validated rodent model of
nausea/malaise), anorexia, and weight loss. Though these data begin to outline a circuit of CNS sites through
which EC-induced malaise and anorexia are mediated, important details of the circuit remain unknown.
Specifically, the functional relevance, neurochemical phenotypes, modulatory inputs, and target projections of
these hindbrain-forebrain neural populations must be directly investigated to uncover novel targets for the
treatment of CINV and energy balance dysregulation. To this end, the innovative approaches in this proposal
combine state-of-the-art neuroscience techniques to [1] investigate the functional role of projection- and cell
type-specific neuron populations in the mediation of CINV and energy dysregulation, [2] examine the
neuropeptide/signaling phenotype(s) and post-synaptic targets of EC-activated CeA neurons, and [3] examine
the modulatory role of central GLP-1 signaling in the NTS, lPBN, and CeA in CINV and energy dysregulation.
The proposed experiments will use and compare non-vomiting and vomiting laboratory animal models to
maximize translational potential of this work. Overall, these studies will expand our understanding of the
mechanisms mediating chemotherapy-induced malaise and energy balance dysregulation by revealing the
neurocircuitry and chemical signals that produce these undesirable side effects. Additionally, results will
identify new target neuron populations and/or neurochemical/peptide systems for the development of novel
treatments of CINV and energy balance dysregulation.

## Key facts

- **NIH application ID:** 9895765
- **Project number:** 5R01DK112812-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Bart C DE JONGHE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,901
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895765

## Citation

> US National Institutes of Health, RePORTER application 9895765, Neural mechanisms of nausea, vomiting, and energy balance dysregulation in animal models (5R01DK112812-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9895765. Licensed CC0.

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