# Mapping brain-wide opioid actions by profiling neuronal activities and in vivo cellular target engagement

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $830,063

## Abstract

Abstract
Opioids are highly effective at reducing pain, but their potential for addiction and overdose has led to a growing
public health crisis. Researchers have attempted to develop new opioid compounds that are less likely to be
abused and have fewer side effects, but these efforts have been difficult. The endogenous opioid system has
multiple receptors and ligands heterogeneously expressed across different parts of the body and cell types.
Tremendous work has been done to delineate the relationships between opioid receptors (ORs) and ligands.
However, the specificity of ligand-receptor engagement often depends on relative affinities at predetermined
targets. In general, in vivo spatial and cellular heterogeneity of the brain obscure opioid actions, making them
hard to predict based on receptor affinity alone.
Currently, single-cell and spatial transcriptomics are transforming our understanding of brain architecture.
However, there is a significant gap in how we measure opioid actions and align them with the spatially resolved
cellular atlas of the brain. Levering emerging CATCH and inverse activity marker (IAM) techniques, we propose
multimodal profiling of opioid actions with spatial and single-cell resolution across the entire mouse brain. Using
three pharmacologically diverse opioids, we aim to map neuronal activities and cellular binding of these drugs
onto the entire mouse brain in an unbiased way and register them with cell types identified from single-cell
transcriptomics. Furthermore, we will test whether a drug’s affinities across different ORs determine its in vivo
cell and neural ensemble engagement. Not only would this project provide a circuit-level mechanism linking the
molecular pharmacology to brain-wide opioid actions, but also lay out a roadmap for evaluating and developing
new opioids, e.g., by incorporating regional and cell-type preference into the structure-activity-relationship for
lead optimization or by revealing on- and off-target sites to guide further cell-type specific in vitro chemical
screening and optimization.

## Key facts

- **NIH application ID:** 10932259
- **Project number:** 5R01DA059393-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Laura M. Bohn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $830,063
- **Award type:** 5
- **Project period:** 2023-09-30 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932259

## Citation

> US National Institutes of Health, RePORTER application 10932259, Mapping brain-wide opioid actions by profiling neuronal activities and in vivo cellular target engagement (5R01DA059393-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10932259. Licensed CC0.

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