# AgRP Neurons as Modulators of Drug Reactivity

> **NIH NIH R03** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $77,322

## Abstract

ABSTRACT
Drug abuse and addiction are serious mental health problems that impose severe economic and social
burdens on our community. It has been known for decades that physiological states (hunger and satiety) can
influence drug seeking, taking, and relapse. Previous studies showed that hunger-mediating hormones
enhance drug use, collectively implying that hunger can be a risk factor for enhanced drug response. However,
the interaction between hunger-mediating neurons and drug response remains unclear. Among multiple
neuronal populations related to hunger, neurons expressing Agouti-related peptide (AgRP) in the arcuate
nucleus of the hypothalamus are known to be a central mediator of hunger. Despite its central role in evoking
hunger, there is a gap in our knowledge of the effect of AgRP neuronal activity on drug response.
Our overall goal is to determine the role of AgRP neurons in modulating drug behavioral responsivity and drug-
directed behavior through recruitment of mesolimbic reward circuitry which, in turn, modulates motor outputs.
As an initial exploratory step, the PI seeks to determine the effect of AgRP neuronal activity on stimulant-driven
motor outputs to measure alterations in behavioral sensitivity to abused drugs using zebrafish larvae as an
optically tractable model. Our central hypothesis is that the activation of AgRP neurons potentiates motor-
neuronal and behavioral responses to psychostimulant drugs. Our specific aim is to determine the effect of
AgRP neuronal activity on stimulant-driven responses. We will use transgenic zebrafish lines that express a
genetically encoded neural activity indicator in spinal motor neurons, and also a genetically encoded
optogenetic actuator or silencer in AgRP neurons. To determine whether the activation of AgRP neurons is
sufficient or necessary to increase drug responses, stimulant-driven motor neuronal activity and behavioral
responses will be monitored while optogenetically activating or suppressing AgRP neurons. A better
understanding of the role of AgRP neurons on drug response could lead to the discovery of novel therapeutic
opportunities that control the AgRP neuronal excitability in order to mitigate drug addiction.

## Key facts

- **NIH application ID:** 10128115
- **Project number:** 1R03DA050962-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Eunjung Erica Jung
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,322
- **Award type:** 1
- **Project period:** 2021-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128115

## Citation

> US National Institutes of Health, RePORTER application 10128115, AgRP Neurons as Modulators of Drug Reactivity (1R03DA050962-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128115. Licensed CC0.

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