Abstract
Nonmedical use of the prescription opioid analgesic oxycodone is a major problem in the United States, particularly among adolescents and young adults. This study characterized self-administration of oxycodone by adolescent and adult mice, and how this affects striatal dopamine levels. Male C57BL/6J mice (4 or 10 weeks old) were allowed to acquire oxycodone self-administration (0.25 mg/kg per infusion) for 9 days, and then tested with varying doses of oxycodone (0, 0.125, 0.25, 0.5, and 0.75 mg/kg per infusion). On completion of the self-administration study, a guide cannula was implanted into the striatum of these mice. Six days later, microdialysis was conducted on the freely moving mouse. After collection of baseline samples, oxycodone was administered i.p. (1.25, 2.5, and 5.0 mg/kg) and samples were collected for 1 h after each dose. Adult mice self-administered significantly more oxycodone across the doses tested. After 1 week, basal striatal dopamine levels were lower in mice of both ages that had self-administered oxycodone than in yoked saline controls. Oxycodone challenge increased striatal dopamine levels in a dose-dependent manner in both age groups. Of interest, the lowest dose of oxycodone led to increased striatal dopamine levels in the mice that had self-administered oxycodone during adolescence but not those that self-administered it as adults. The lower number of infusions of oxycodone self-administered by adolescent mice, and their later increased striatal dopamine in response to the lowest dose of oxycodone (not found in adults), suggest differential sensitivity to the reinforcing and neurobiological effects of oxycodone in the younger mice.
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This work was supported by NIH-NIDA P60 DA05130 to Dr Mary Jeanne Kreek.
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The authors declare that, except for income received from the 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., Picetti, R., Butelman, E. et al. Behavioral and Neurochemical Changes Induced by Oxycodone Differ Between Adolescent and Adult Mice. Neuropsychopharmacol 34, 912–922 (2009). https://doi.org/10.1038/npp.2008.134
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DOI: https://doi.org/10.1038/npp.2008.134
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