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Validation and characterization of oxycodone physical dependence in C57BL/6J mice
Moriah Carper1, Katherine M Contreras1, D Matthew Walentiny1
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
European Journal of Pharmacology
|April 26, 2021
Summary
This study validates a mouse model for oxycodone dependence, crucial for developing treatments for opioid use disorder. The model effectively demonstrates withdrawal symptoms and their reversal, aiding in the evaluation of new medications.
Area of Science:
- Pharmacology
- Neuroscience
- Addiction Research
Background:
- Opioid use disorder (OUD) is a significant public health issue in the US.
- Preclinical models are essential for understanding opioid dependence and testing treatments.
- Existing models often focus on morphine, with fewer on contemporary prescription opioids like oxycodone.
Purpose of the Study:
- To characterize and validate a mouse model for oxycodone dependence.
- To establish paradigms for both spontaneous and precipitated withdrawal.
- To provide a platform for evaluating potential therapeutics for OUD.
Main Methods:
- Male C57BL/6J mice received escalating doses of oxycodone or saline twice daily for 8 days.
- Withdrawal signs were precipitated by naloxone challenge or observed during spontaneous withdrawal.
- Somatic signs were measured at various time points post-withdrawal.
- Mice were pretreated with oxycodone or clonidine to assess their effect on withdrawal symptoms.
Main Results:
- Oxycodone or clonidine pretreatment dose-dependently attenuated somatic withdrawal signs.
- Mice exhibited increased withdrawal signs during spontaneous withdrawal at 24 hours post-cessation.
- Precipitated withdrawal following naloxone challenge showed peak signs at 6 hours and were significantly elevated across all time points compared to controls.
- The model demonstrated reversal of withdrawal effects by positive controls.
Conclusions:
- The developed mouse model reliably replicates key features of oxycodone dependence and withdrawal.
- This validated model serves as a crucial tool for preclinical screening of novel medications targeting opioid withdrawal symptoms.
- It facilitates research into the neurobiological mechanisms underlying opioid physical dependence.
