# Opioidergic mechanisms underlying cocaine conditioned reinforcement

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $38,185

## Abstract

Project summary/abstract:
Cocaine use disorder affects nearly one million Americans, yet there are no current approved therapeutics for
effective treatment or to prevent relapse. Major contributors to relapse are drug paired cues that can elicit feelings
of craving in humans and lead to drug seeking. The ability of cues to maintain drug seeking behavior after
sufficient number of cue and cocaine pairings is termed the conditioned reinforcing effects of cocaine. Previous
work suggests that dopaminergic and glutamatergic systems in reward circuitry are involved, and other studies
have implicated the endogenous opioid system, particularly in the nucleus accumbens, in mediating behavior
elicited by cocaine-paired cues. Specifically, blocking opioid receptor activation attenuates drug seeking
behavior. Similarly, increases in levels of enkephalin, an endogenous opioid peptide, in the nucleus accumbens
have been shown with some primary reinforcers and can lead to reinstatement of drug seeking. Little is known
about the role of endogenous opioids in conditioned reinforcement nor the opioidergic mechanisms contributing
to this complex behavior. To gain insights into the contribution of the endogenous opioid system in addiction and
specifically in cocaine-paired cues, I will explore the enkephalinergic response to cues and opioid receptor
activation modulating these effects. The current proposal is supported by our preliminary studies that activation
of the delta opioid receptor (DOR) potentiates operant responding for drug-paired cues, indicating an increase
in conditioned reinforcement. Here I will test the central hypothesis that presentation of cues that have acquired
conditioned reinforcing properties lead to an increase of enkephalin in the nucleus accumbens shell that acts on
DORs to drive operant responding for cocaine-paired cues. This work will 1) measure and potentiate enkephalin
levels and 2) manipulate opioid receptor activation pharmacologically in the nucleus accumbens during a
stringent test of cocaine conditioned reinforcement. This work will lead to better understanding of and insight into
the underlying mechanisms behind the conditioned reinforcing properties of cocaine cues. This proposal will
provide me essential training in 1) in vivo neuropeptide collection, 2) pharmacological manipulation of the
endogenous opioid system, and 3) rigorous behavioral experiments in addiction research. The skills and training
opportunities described in this proposal will enable me to be a successful professional scientist working in drug
development to identify novel therapeutics for neurological disorders.

## Key facts

- **NIH application ID:** 10229240
- **Project number:** 1F31DA053697-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Lauren Grace Rysztak
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,185
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229240

## Citation

> US National Institutes of Health, RePORTER application 10229240, Opioidergic mechanisms underlying cocaine conditioned reinforcement (1F31DA053697-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10229240. Licensed CC0.

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