Characterization and validation of a spontaneous acute and protracted oxycodone withdrawal model in male and female mice

Katherine M Contreras ¹, Belle Buzzi ¹, Julian Vaughn ¹

⁰Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.

Pharmacology, Biochemistry, and Behavior +

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June 4, 2024

View abstract on PubMed

Summary

This study validates a new mouse model for oxycodone dependence, crucial for understanding opioid use disorder (OUD). The model shows distinct physical and behavioral withdrawal signs, aiding in developing new treatments for OUD.

Area Of Science

Neuroscience
Pharmacology
Behavioral Science

Background

Opioid use disorder (OUD) presents significant health challenges, often co-occurring with affective disorders.
Preclinical models are vital for investigating OUD neurobiology and developing effective pharmacotherapies.
Traditional models often use morphine and opioid antagonists, but oxycodone dependence models are needed.

Purpose Of The Study

To develop and validate a novel preclinical model of oxycodone dependence in mice.
To characterize spontaneous withdrawal signs, including somatic, sensory, and anxiety-like behaviors.
To assess the efficacy of clinically approved medications in reversing these withdrawal signs.

Main Methods

Chronic oxycodone administration via osmotic minipumps for 7 days in C57BL/6J mice.
Measurement of somatic withdrawal signs at various time points post-minipump removal.
Assessment of mechanical, thermal, and cold hypersensitivity, and anxiety-like behaviors.

Main Results

Oxycodone discontinuation induced significant somatic withdrawal signs at 60 and 120 mg/kg/day doses.
Withdrawal signs were reversed by clinically approved medications for OUD.
Spontaneous withdrawal led to persistent mechanical and cold hypersensitivity and anxiety-like behaviors in both male and female mice.

Conclusions

This study successfully validated a new mouse model for oxycodone dependence.
The model exhibits temporally distinct somatic, hyperalgesic, and anxiety-like behaviors during spontaneous withdrawal.
This validated model offers a valuable tool for mechanistic and translational research in opioid dependence.

Keywords:

Anxiety-like behaviors Mice Oxycodone Withdrawal