# Pharmacological interactions between conventional and biased MOR agonists

> **NIH NIH F32** · UNIVERSITY OF FLORIDA · 2021 · $9,000

## Abstract

PROJECT SUMMARY
Our laboratory focuses on understanding how different ligands can modulate the activity of the mu opioid receptor
(MOR) and how differential activation may preserve or prevent physiological responses typically induced by
drugs at this receptor. To this end, the Bohn lab has worked to develop diverse “biased” agonists that diverge
from morphine and enkephalins by their ability to preferentially signal through G protein pathways over recruiting
βarrestin2 to the receptor. Our preliminary studies suggest that SR-17018, our most G biased compound, does
not induce respiratory suppression in mice, although it has the same potency as morphine in the hot plate
nociception assay. Further, unlike morphine, which stimulates mouse running behavior, SR-17018 does not
induce hyperactivity. When we treat mice with SR-17018 and morphine, we find that SR-17018 blocks morphine-
induced hyperactivity. I will continue characterizing the behavioral responses using MOR agonists from βarrestin
2- and G protein-biased ligands, in a dose-response manner in the locomotor activity assay and respiratory
suppression to fully understand the nature of this apparent competitive interaction.
This proposal aims to attain training in behavioral and in vitro pharmacology to define opioid interactions at MOR
in mice. I will gain training in execution and design of behavioral studies, acquisition of pharmacokinetic data,
and evaluation of receptor signaling in brain regions. Further, my training will entail gaining understanding in
fundamentals of GPCR pharmacological principles. I will use mouse models of drug reinforcement initially; my
training in understanding addictive behaviors will be augmented by taking a formal course on the neurobiology
of addiction and by participating in focused addiction research conferences outlined in the proposal. The studies
resulting from this application will be used to identify possible benefits for adjuvant therapy to potentiate
antinociception while decreasing the risk of adverse effects. These studies will shed light on the role and
mechanism of biased agonism in mice towards the development of safer pain treatment and pharmaceuticals
and will provide me the training that I need to continue my career path towards becoming an independent faculty
researcher in addiction sciences.

## Key facts

- **NIH application ID:** 10596345
- **Project number:** 6F32DA052124-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** AGNES M ACEVEDO-CANABAL
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,000
- **Award type:** 6
- **Project period:** 2020-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596345

## Citation

> US National Institutes of Health, RePORTER application 10596345, Pharmacological interactions between conventional and biased MOR agonists (6F32DA052124-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10596345. Licensed CC0.

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