# Monitoring Real-Time Neuropeptide Dynamics

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $378,873

## Abstract

ABSTRACT:
The role of mesolimbic opioid peptides in motivated behavior and reward-related decision making is
unclear, despite extensive evidence indicating that these molecules are important mediators of hedonic
and motivational aspects of reward processing, and the fundamental response to drugs of abuse. This
is largely due to a critical gap in understanding when and where these molecules are released,
because there is a paucity of detection methods for monitoring opioid peptides in the extracellular
space. We have established the feasibility of using fast-scan cyclic voltammetry (FSCV) and carbon-
fiber microelectrodes in tissue for the detection of endogenous enkephalin (ENK) fluctuations in real time.
The objective of this proposal is to optimize and fully characterize this methodology, so as to provide the
community with an established tool that can be used to study the role of the ENKs in complex physiological
processes ranging from basic endocrine function to motivation. The first goal is to fully characterize
selectivity. We will assess incorporation of well-characterized Nafion composite membranes into the
sensor design as a physical means to enhance selective detection. We will also investigate the
electrochemistry of each of 20 natural amino acids individually, and use these data in a multivariate
approach to identify individual amino acid contributors to the voltammetric signal when these residues are
incorporated into longer amino acid chains. The second goal is to optimize sensitivity by systematically
investigating electrochemical parameters (scan rates, holding potentials, and sampling frequencies), as
well as promising nanoscale electrode materials. Finally, the third goal is to evaluate real-time ENK
dynamics in rat adrenal and brain tissue, so as to provide insight into the normal concentration range,
extracellular lifetime, and diffusion profile (sphere of influence) of the ENKs, as well as physiological and
pharmacological conditions that can induce changes in peptidergic signaling. We will also directly compare
the stimulation-response relationship for small molecule transmitters and ENK, using FSCV. This project is
a critical step toward our long-term goal of elucidating how the release and clearance dynamics of
several neuropeptides and small molecules underlie discrete aspects of motivated behavior. It will
clarify outstanding questions regarding the fundamental nature of endogenous opioid peptide signaling, and
enable FSCV to be used confidently to reveal critical mechanistic details that will inform evidence-based
pharmacotherapies for treating a wide range of disorders, including substance abuse disorders.

## Key facts

- **NIH application ID:** 9978009
- **Project number:** 5R01DA043007-04
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** LESLIE A SOMBERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,873
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978009

## Citation

> US National Institutes of Health, RePORTER application 9978009, Monitoring Real-Time Neuropeptide Dynamics (5R01DA043007-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9978009. Licensed CC0.

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