# Role for Tas2Rs in opioid addiction

> **NIH NIH R37** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $169,498

## Abstract

Project Summary:
Opioid drugs such as oxycodone are thought to act on addiction-relevant brain circuits
exclusively through opioid receptors, most notably the μ opioid receptors (MORs). In common
with other addictive drugs, morphine is a plant-derived alkaloid with an innately aversive bitter
taste, a sensory modality that evolved to protect against ingestion of potentially
noxious substances. Synthetic and semisynthetic opioids such as oxycodone also have alkaloid
structures and a bitter taste. Taste 2 receptors (T2Rs) evolved to detect potentially poisonous
alkaloids, but their potential involvement in the addiction-related behavioral actions of opioids is
unknown to nicotine. Recently, we established a key role for T2Rs in regulating the aversive
behavioral actions of nicotine that motivate nicotine avoidance and protect against addiction.
Here, we will explore the role for T2Rs in regulating avoidance of opioids. T2Rs signal through a
specialized G protein called α-gustducin, which is derived from the Gnat3 gene. In Experiment
1, we will assess the rewarding and aversive properties of oxycodone in wild-type and Gnat3-/-
 mice using conditioned place preference and avoidance conditioning. In Experiment 2, we will
assess the reinforcing properties of oxycodone in wild-type and Gnat3-/- mice using the
intravenous self-administration procedure. In Experiment 3, we will assess physical and
affective components of opioid withdrawal in oxycodone-dependent wild-type and Gnat3-/- mice.
In Experiment 4, we will determine which subtypes of T2Rs `cmehosense' oxycodone and other
opioid drugs. These experiments have the potential to establish an entirely new class of
receptors that can be targeted for the development of novel addiction therapeutics.

## Key facts

- **NIH application ID:** 10177030
- **Project number:** 3R37DA020686-13S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Paul J. Kenny
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,498
- **Award type:** 3
- **Project period:** 2020-07-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177030

## Citation

> US National Institutes of Health, RePORTER application 10177030, Role for Tas2Rs in opioid addiction (3R37DA020686-13S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177030. Licensed CC0.

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