# Endogenous enkephalins and reward mechanisms

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $306,740

## Abstract

Project Summary/Abstract
There are fundamental gaps in our understanding of the neurobiological processes involved in addiction, in
particular the complex changes produced by drug-paired cues (conditioned reinforcers) that increase drug-taking
behavior and provoke relapse. Identifying novel mechanisms by which conditioned reinforcers modify behavior
is essential for future efforts to design new treatments to control drug craving and prevent relapse to addiction.
The long-term goal of this work is to further our understanding of the behavioral and neurobiological mechanisms
mediating drug-paired stimuli that serve as conditioned reinforcers. The objective of this application is to identify
the role of the endogenous enkephalinergic system in regulating the reinforcing properties of cocaine-associated
stimuli that are an essential part of cocaine addiction. Enkephalins binds with high affinity to delta-opioid
receptors (DOPRs), which are highly expressed within the reward pathway, and DOPR activation can alter
responding for drug-paired cues without primary reinforcing effects. Our overarching hypothesis is that
enkephalins acting at delta-opioid receptors (DOPRs) in the nucleus accumbens shell (NAc-S) play an essential
role in the behavioral and neurochemical mechanisms mediating the conditioned reinforcing properties of
cocaine-paired cues. This proposal will couple behavioral measurements of conditioned reinforcement with in
vivo microdialysis and comprehensive mass spectrometry analysis to evaluate in real-time the role of the
enkephalin and DOPRs in establishing and maintaining the salience of cocaine-associated cues. Through the
innovative use of behavioral and neurochemical measurement techniques, this proposal will expand beyond the
status quo to investigate novel mechanisms selectively mediating conditioned reinforcement but not necessarily
the direct, primary reinforcing effects of cocaine. Ultimately, such knowledge has the potential to develop new
treatments for preventing relapse.

## Key facts

- **NIH application ID:** 10203896
- **Project number:** 5R01DA042092-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** EMILY M JUTKIEWICZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $306,740
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203896

## Citation

> US National Institutes of Health, RePORTER application 10203896, Endogenous enkephalins and reward mechanisms (5R01DA042092-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10203896. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*