Oral oxycodone self‐administration leads to features of opioid misuse in male and female mice

• Published in: Addiction biology Vol. 28; no. 1; pp. e13253 - n/a
• Main Authors: Slivicki, Richard A., Earnest, Tom, Chang, Yu‐Hsuan, Pareta, Rajesh, Casey, Eric, Li, Jun‐Nan, Tooley, Jessica, Abiraman, Kavitha, Vachez, Yvan M., Wolf, Drew K., Sackey, Jason T., Kumar Pitchai, Dhinesh, Moore, Terrill, Gereau, Robert W., Copits, Bryan A., Kravitz, Alexxai V., Creed, Meaghan C.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2023; Wiley
• Subjects: Abuse; Analgesics, Opioid - therapeutic use; Animals; Drug abuse; Drug addiction; Female; Fentanyl; Life Sciences; Male; Mice; Morphine; Narcotics; opioid addiction; Opioid-Related Disorders - drug therapy; Opioids; Oral administration; oral self‐administration; Oxycodone; Pharmacokinetics; Reinforcement, Psychology; Reinstatement; Sweeteners; Withdrawal; oxycodone; oral self-administration; opioid addiction
• ISSN: 1355-6215; 1369-1600; 1369-1600
• DOI: 10.1111/adb.13253

Use of prescription opioids, particularly oxycodone, is an initiating factor driving the current opioid epidemic. There are several challenges with modelling oxycodone abuse. First, prescription opioids including oxycodone are orally self‐administered and have different pharmacokinetics and dynamics than morphine or fentanyl, which have been more commonly used in rodent research. This oral route of administration determines the pharmacokinetic profile, which then influences the establishment of drug‐reinforcement associations in animals. Moreover, the pattern of intake and the environment in which addictive drugs are self‐administered are critical determinants of the levels of drug intake, of behavioural sensitization and of propensity to relapse behaviour. These are all important considerations when modelling prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we designed an oral, homecage‐based oxycodone self‐administration paradigm. Mice voluntarily self‐administer oxycodone in this paradigm without any taste modification such as sweeteners, and the majority exhibit preference for oxycodone, escalation of intake, physical signs of dependence and reinstatement of seeking after withdrawal. In addition, a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model is therefore translationally relevant and useful for studying the neurobiological substrates of prescription opioid abuse. Mice readily orally self‐administer oxycodone and escalate intake over time. This oral self‐administration results in features of opioid use disorder including physical withdrawal signs, drug seeking in extinction and continuation of intake despite negative consequences. This model provides a high‐throughput option for well‐powered studies to model features of prescription oxycodone abuse in mice.