Abstract
Introduction
Non-medical use of prescription opioids such as the mu opioid receptor (MOP-r) agonist oxycodone is a growing problem in the USA and elsewhere. There is limited information about oxycodone’s impact on diverse gene systems in the brain.
Objectives
The current study was designed to examine how chronic oxycodone self-administration (SA) affects gene expression in the terminal areas of the nigrostriatal and mesolimbic dopaminergic pathways in mice.
Method
Adult male C57BL/6J mice underwent a 14-day oxycodone self-administration procedure (4 h/day, 0.25 mg/kg/infusion, FR1) and were euthanized 1 h after the last session. The dorsal and ventral striata were dissected, and total RNAs were extracted. Gene expressions were examined using RNA sequencing.
Result
We found that oxycodone self-administration exposure led to alterations of expression in numerous genes related to inflammation/immune functions in the dorsal striatum (54 upregulated genes and 1 downregulated gene) and ventral striatum (126 upregulated genes and 15 downregulated genes), with 38 upregulated genes identified in both brain regions.
Conclusion
This study reveals novel neurobiological mechanisms underlying some of the effects of a commonly abused prescription opioid. We propose that inflammation/immune gene systems may undergo a major change during chronic self-administration of oxycodone.
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Acknowledgments
This work was supported by NIH 1R01DA029147 (YZ) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (MJK). Y. Liang is supported by the NIH Center for Clinical and Translational Science Award (CTSA) and the National Center for Advancing Sciences (NCATS).
We thank Dr. Yuval Itan from Dr. Jean-Laurent Casanova’s laboratory at the Rockefeller University for his help with the functional enrichment analyses.
We thank Dr. Tom Rogers for his interpretation of the data and suggestions for this manuscript.
We thank Dr. Ann Ho, Dr. Eduardo Butelman, and Susan Russo for proofreading the manuscript.
We thank Dr. Kyle Windisch for her assistance in manuscript preparation.
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Animal care and experimental procedures were conducted according to the Guide for the Care and Use of Laboratory Animals. The experimental protocols used were approved by the Institutional Animal Care and Use Committee of the Rockefeller University.
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The authors declare that, except for income received from our primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
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Zhang, Y., Liang, Y., Levran, O. et al. Alterations of expression of inflammation/immune-related genes in the dorsal and ventral striatum of adult C57BL/6J mice following chronic oxycodone self-administration: a RNA sequencing study. Psychopharmacology 234, 2259–2275 (2017). https://doi.org/10.1007/s00213-017-4657-y
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DOI: https://doi.org/10.1007/s00213-017-4657-y