Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

Rachel D. Altshuler, Eddy S. Yang, Kristine T. Garcia, Ian R. Davis, Adedayo Olaniran, Meron Haile, Syrus Razavi, Xuan Li

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


One of the main challenges in treating opioid-use disorders is relapse during abstinence, triggered by re-exposure to drug-associated cues. Previous studies have demonstrated that drug-seeking in rats progressively increases over time during withdrawal (incubation of drug craving). Here, we used male rats and examined neural mechanisms underlying incubation of craving to oxycodone, a commonly abused prescription opioid, and we focused on orbitofrontal cortex (OFC), a brain region previously implicated in incubation of heroin craving. We first used neuronal activity marker Fos and measured neuronal activation in OFC (ventral and lateral OFC) associated with day-1 and day-15 relapse tests. Next, we determined the effect of pharmacological reversible inactivation of OFC on incubated oxycodone seeking on withdrawal day 15. Finally, we determined the effect of reversible inactivation of OFC on nonincubated oxycodone seeking on withdrawal day 1. We found that lever presses during relapse tests were higher on withdrawal day 15 than on withdrawal day 1 (incubation of oxycodone craving). Incubation of oxycodone craving is accompanied with a time-dependent increase of Fos protein expression in both ventral and lateral OFC. Lastly, OFC inactivation decreased oxycodone seeking on withdrawal day 15 but had no effect on withdrawal day 1. Together with the previous heroin study, results here show that OFC plays a critical role in incubation of opioid craving.

Original languageEnglish
Article numbere12927
JournalAddiction Biology
Issue number2
StatePublished - Mar 2021

Bibliographical note

Funding Information:
This research is supported by University of Maryland Department of Psychology Startup Funds (X.L.). The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript. We thank Dr Yavin Shaham for supporting the initiation of this project. We thank Trinity Russell for technical support during the early phase of this project.

Publisher Copyright:
© 2020 Society for the Study of Addiction


  • Fos
  • incubation of craving
  • orbitofrontal cortex
  • oxycodone
  • relapse
  • self-administration

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health


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