# Preclinical Trial: Targeting the Neuropeptide S Receptor to Curb Opioid Taking and Seeking

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $419,876

## Abstract

Summary
Substance use disorders have a devastating impact on individuals, families, and society. Present
pharmacological treatments do not fully ameliorate patients’ symptoms and in many cases are unable to treat
the full spectrum of symptoms. Therefore, it is paramount to identify new targets for pharmacological
intervention. To do this we must better understand the neural mechanisms underpinning drug-mediated
reward, persistent drug-taking and relapse behavior.
The Neuropeptide S (NPS) receptor when activated in rats facilitates reward-related behaviors (e.g. cocaine
seeking). Paradoxically, NPS receptor activation is also anxiolytic-like. As part of our drug discovery efforts, a
NPS receptor targeted molecule was found that retains the anxiolytic-like properties but reduces cocaine
seeking behaviors. In regard to opioids, the levels of NPS receptor changes in rats that have been made
dependent on morphine, and levels of the receptor further change after withdrawal. Therefore, the data
suggest that the NPS-system may be a prime target for addressing the unmet therapeutic need of substance
use disorders. To understand the mechanism by which NPS receptor targeted molecules produce their effects,
the fundamental circuit pathway and behavioral analyses need to be completed.
The goals of this project are proof of concept that NPS receptor targeted molecules can mitigate opioid
seeking. And, whether these same molecules can 1) reduce oxycodone taking and 2) reduce the motivation to
obtain oxycodone. Ultimately, knowledge gained through these experiments will allow for the determination of
the therapeutic potential of the NPS receptor as a target for mitigating substance use disorders.

## Key facts

- **NIH application ID:** 11020387
- **Project number:** 1R21DA061784-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Stewart Donaldson Clark
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $419,876
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11020387

## Citation

> US National Institutes of Health, RePORTER application 11020387, Preclinical Trial: Targeting the Neuropeptide S Receptor to Curb Opioid Taking and Seeking (1R21DA061784-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11020387. Licensed CC0.

---

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