Abstract
Rationale
Over the last decade, oxycodone has become one of the most widely abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem that has prompted a need to develop animal models of OUD that have both face and predictive validity. Oxycodone use in humans is more prevalent in women and leads to pronounced hyperalgesia and irritability during withdrawal. However, unclear is whether current animal models of oxycodone self-administration recapitulate these characteristics in humans.
Objectives
We assessed the face validity of a model of extended-access oxycodone self-administration in rats by examining the escalation of oxycodone intake and behavioral symptoms of withdrawal, including irritability-like behavior and mechanical nociception, in male and female Wistar rats.
Results
Both male and female rats escalated their oxycodone intake over fourteen 12-h self-administration sessions. After escalation, female rats administered more drug than male rats. No differences in plasma oxycodone levels were identified, but males had a significantly higher level of oxycodone in the brain at 30 min. Extended access to oxycodone significantly decreased aggressive-like behavior and increased defensive-like behaviors when tested immediately after a 12-h self-administration session, followed by a rebound increase in aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception thresholds during withdrawal indicated pronounced hyperalgesia. No sex differences in irritability-like behavior or pain sensitivity were observed.
Conclusions
The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.
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The authors thank Michael Arends for proofreading the manuscript.
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This work was supported by National Institutes of Health grants DA044451, DA043799, AA007456, and AA027301, the Sigrid Juselius Foundation, and the Pearson Center for Alcoholism and Addiction Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Kimbrough, A., Kononoff, J., Simpson, S. et al. Oxycodone self-administration and withdrawal behaviors in male and female Wistar rats. Psychopharmacology 237, 1545–1555 (2020). https://doi.org/10.1007/s00213-020-05479-y
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DOI: https://doi.org/10.1007/s00213-020-05479-y