Modeling features of addiction with an oral oxycodone self-administration paradigm
Modeling features of addiction with an oral oxycodone self-administration paradigm
Abstract Prescription opioid use is an initiating factor driving the current opioid epidemic. There are several challenges with modeling prescription opioid addiction. First, prescription opioids such as oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl. This oral route of administration determines the pharmacokinetic profile, which is critical for establishing reliable drug-reinforcement associations in animals. Moreover, the pattern of intake and environment in which addictive drugs are self-administered intake are critical determinants of the levels of drug intake, sensitization and relapse behavior. This is an important consideration with 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 present an oral oxycodone self-administration paradigm that is administered in the home cage. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and exhibit preference for oxycodone, escalation of intake, physical signs of dependence, reinstatement of seeking after withdrawal, and a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model could be useful for studying the neurobiological substrates specifically relevant to prescription opioid abuse.
Copits Bryan A.、Kravitz Alexxai V.、Abiraman Kavitha、Gereau Robert W. IV、Slivicki Richard A.、Tooley Jessica、Vachez Yvan M.、Li Jun-Nan、Murphy Caitlin A.、Pareta Rajesh、Chang Yu-Hsuan、Earnest Tom、Creed Meaghan C.
Washington University Pain Center, Dept. of Anesthesiology, Washington University in St. Louis||Department of Neuroscience, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. Louis||Department of Psychiatry, Washington University in St. Louis||Department of Neuroscience, Washington University in St. Louis||Department of Biomedical Engineering, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. Louis||Department of Neuroscience, Washington University in St. Louis||Department of Biomedical Engineering, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. LouisWashington University Pain Center, Dept. of Anesthesiology, Washington University in St. Louis||Department of Psychiatry, Washington University in St. Louis||Department of Neuroscience, Washington University in St. Louis||Department of Biomedical Engineering, Washington University in St. Louis
医学研究方法基础医学神经病学、精神病学
Copits Bryan A.,Kravitz Alexxai V.,Abiraman Kavitha,Gereau Robert W. IV,Slivicki Richard A.,Tooley Jessica,Vachez Yvan M.,Li Jun-Nan,Murphy Caitlin A.,Pareta Rajesh,Chang Yu-Hsuan,Earnest Tom,Creed Meaghan C..Modeling features of addiction with an oral oxycodone self-administration paradigm[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.02.08.430180.点此复制
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