# Interrogating the cholinergic basis of opioid use disorder

> **NIH NIH R61** · DUKE UNIVERSITY · 2020 · $483,000

## Abstract

ABSTRACT: Interrogating the cholinergic basis of opioid use disorder
Opioids offer unmatched clinical efficacy in the treatment of pain, and offer pronounced therapeutic potential in
the treatment of anxiety, depression, and psychosis. Nevertheless opioids come with equally harmful side effects
that can lead to opioid use disorder. Three major subtypes of opioid receptors have been identified, which are
each expressed in numerous cells. Because traditional drugs impact all cells in a given volume, it has been
difficult to map cell type-specific contributions of drug-mediated behavior. To address this gap, we developed
DART
(drugs acutely restricted by tethering), which works by genetically programming a subset of cells to capture
and concentrate a specific drug to levels ~1000 times higher than anywhere else, thus restricting drug action to
the chosen subset of cells. Here, we propose to develop, characterize, and distribute a comprehensive toolset
focused on opioid neuropharmacology. As a roadmap for the widespread adoption of these reagents, we propose
behavioral experiments motivated by a recent double-blind placebo-controlled trial in which a cholinergic drug
demonstrated efficacy in the treatment of opioid use disorder. We will test the hypothesis that μORs on
cholinergic interneurons mediate the harmful (addictive) effects of opioids, independent of helpful (analgesic)
effects. The proposed technologies will offer the unprecedented opportunity to establish causal behavioral roles
of opioid neuropharmaceuticals mediated by defined cell types. Because the technologies are rooted in
therapeutically relevant neuropharmaceuticals, clinical relevance is provided without the need to sacrifice
mechanistic rigor.

## Key facts

- **NIH application ID:** 10044348
- **Project number:** 1R61DA051530-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Michael R Tadross
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $483,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044348

## Citation

> US National Institutes of Health, RePORTER application 10044348, Interrogating the cholinergic basis of opioid use disorder (1R61DA051530-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10044348. Licensed CC0.

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