# Nociceptin receptor signaling and regulation of dopamine transmission in drug reward circuitry

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $143,048

## Abstract

Project Summary
The overall goal of this research is to determine how the nociceptin receptor (NOPR) modulates dopamine
(DA) transmission and behavioral responses associated with drug addiction. Central administration of NOPR
agonists inhibits the rewarding effects of commonly abused drugs including cocaine, morphine, amphetamine,
and alcohol in conditioned place preference assays. NOPR is widely expressed in the brain, but preliminary
data shows that NOPR activation in DA neurons of the ventral tegmental area (VTA) is sufficient to inhibit
cocaine preference. We hypothesize that this effect is due to the demonstrated ability of NOPR activation to
inhibit DA transmission to the nucleus accumbens. However, NOPR signaling has never been studied directly
in midbrain DA neurons, and how it regulates DA transmission is unknown. The research objectives of this five
year K01 award are: (1) to determine the intracellular signaling responses generated by NOPR activation in
real-time within midbrain DA neurons, (2) to identify cellular and molecular mechanisms that control NOPR
desensitization and internalization in midbrain DA neurons, and (3) to determine how NOPR signaling
suppresses cocaine-induced increases in dopamine transmission. I have expertise in techniques for
subcellular optogenetic manipulation and measurement of G protein coupled receptor (GPCR)-mediated
signaling that make me uniquely qualified to achieve these aims. However, I require additional training in the
use of primary neuronal cultures, genetic and viral methods, and for measuring dopamine uptake and
dopamine transporter trafficking. My outstanding co-mentors, Drs. Michael Bruchas and N. Gautam, as well as
our collaborators here at Washington University School of medicine will provide the required training.
Washington University School of Medicine. Successful completion of my research and training goals, and my
transition to scientific independence, will be ensured through regular interactions with my co-mentors, as well
as my in-house advisory committee including Drs. Karen O'Malley, Robert Gereau, and Theodore Cicero.
Overall, this Mentored Research Scientist Development Award will greatly facilitate my goal to establish myself
as a leading contributor to our understanding of GPCR regulation of neurotransmission in reward and addiction
circuitry.

## Key facts

- **NIH application ID:** 10112864
- **Project number:** 5K01DA042219-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Patrick Ross O'Neill
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $143,048
- **Award type:** 5
- **Project period:** 2017-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112864

## Citation

> US National Institutes of Health, RePORTER application 10112864, Nociceptin receptor signaling and regulation of dopamine transmission in drug reward circuitry (5K01DA042219-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10112864. Licensed CC0.

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