# NOP Receptors in nonhuman primate models of AUD

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $502,638

## Abstract

PROJECT SUMMARY.
Alcohol use disorder (AUD) persists as a costly public health problem that lacks widely effective medications.
The scientific premise of the proposed research is that brain receptors for the nociceptin/orphanin FQ peptide
(NOP) are promising targets for new medications, but translational studies in sophisticated nonhuman primate
(NHP) models are needed to inform and direct drug development and clinical testing. This premise is based on
encouraging data from rodent models and positive preliminary data from our NHP laboratory using
buprenorphine and its derivative BU08028, termed a “bifunctional” MOP/NOP agonist because it stimulates
both NOP and mu opioid peptide (MOP) receptors. The proposed studies combine a well-characterized,
clinically relevant NHP model of chronic ethanol (EtOH) drinking, novel NOP- and MOP/NOP-acting drugs, a
translational method of pharmacotherapy assessment and noninvasive brain imaging using positron emission
tomography (PET imaging). After being induced to drink EtOH using established procedures, male and female
rhesus monkeys will have free access to EtOH; responding to receive food pellets will also be monitored as an
index of potential side effects. Specific Aim 1 will determine the effects of buprenorphine and its derivative
BU08028, in combination with drugs that selectively stimulate or block MOP or NOP receptors. The results will
reveal the relative contribution of MOP and NOP receptor stimulation to the ability of bifunctional agonists to
decrease EtOH drinking, indicating the ideal pharmacological profile for a medication. Next (Aim 2), drugs that
possess the desired profile will be selected from among a catalog of novel compounds synthesized by Co-
Investigator Dr. Stephen Husbands. Candidates will be administered daily for several months and effects on
moderate and heavy drinking (6 or 22 hours per day, respectively) will be determined using a translational
approach developed by the P.I. We expect to identify a compound that produces prolonged suppression of
EtOH drinking without altering food-maintained responding or producing adverse effects. Aim 3 consists of
PET imaging studies using the novel radiotracer [11C]NOP-1A that run parallel to Aims 1 and 2. These studies
will characterize (1) the influence of basal NOP receptor availability on initial sensitivity to EtOH, (2) the effects
of long-term EtOH drinking on NOP receptors, (3) the effects of efficacious treatments on NOP receptor
availability, (4) the extent of recovery of NOP receptor availability during abstinence from EtOH and,
importantly, (5) sex differences in all these measures. Together, the results of these studies will provide novel,
translational data to support the feasibility and efficacy of developing MOP/NOP and NOP-selective agonists
as novel AUD pharmacotherapies using translational, clinically relevant NHP models.

## Key facts

- **NIH application ID:** 10212896
- **Project number:** 5R01AA027556-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Paul W. Czoty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $502,638
- **Award type:** 5
- **Project period:** 2020-07-10 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212896

## Citation

> US National Institutes of Health, RePORTER application 10212896, NOP Receptors in nonhuman primate models of AUD (5R01AA027556-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212896. Licensed CC0.

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