Impact of Δ 9 -Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice.
| العنوان: | Impact of Δ 9 -Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice. |
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| المؤلفون: | Slivicki RA; Washington University Pain Center and Department of Anesthesiology, Washington University, St. Louis, MO., Wang JG; Washington University Pain Center and Department of Anesthesiology, Washington University, St. Louis, MO.; Neuroscience Graduate Program, Division of Biology & Biomedical Sciences, Washington University, St. Louis, MO., Nhat VTT; Washington University Pain Center and Department of Anesthesiology, Washington University, St. Louis, MO., Kravitz AV; Washington University Pain Center and Department of Anesthesiology, Washington University, St. Louis, MO.; Department of Psychiatry, Washington University, St. Louis, MO.; Department of Neuroscience, Washington University, St. Louis, MO., Creed MC; Washington University Pain Center and Department of Anesthesiology, Washington University, St. Louis, MO.; Department of Neuroscience, Washington University, St. Louis, MO., Gereau RW 4th; Washington University Pain Center and Department of Anesthesiology, Washington University, St. Louis, MO.; Department of Neuroscience, Washington University, St. Louis, MO.; Department of Biomedical Engineering, Washington University, St. Louis, MO. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 06. Date of Electronic Publication: 2023 Dec 06. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Oxycodone is commonly prescribed for moderate to severe pain disorders. While efficacious, long-term use can result in tolerance, physical dependence, and the development of opioid use disorder. Cannabis and its derivatives such as Δ 9 -Tetrahydrocannabinol (Δ 9 -THC) have been reported to enhance oxycodone analgesia in animal models and in humans. However, it remains unclear if Δ 9 -THC may facilitate unwanted aspects of oxycodone intake, such as tolerance, dependence, and reward at analgesic doses. This study sought to evaluate the impact of co-administration of Δ 9 -THC and oxycodone across behavioral measures related to antinociception, dependence, circadian activity, and reward in both male and female mice. Oxycodone and Δ 9 -THC produced dose-dependent antinociceptive effects in the hotplate assay that were similar between sexes. Repeated treatment (twice daily for 5 days) resulted in antinociceptive tolerance. Combination treatment of oxycodone and Δ 9 -THC produced a greater antinociceptive effect than either administered alone, and delayed the development of antinociceptive tolerance. Repeated treatment with oxycodone produced physical dependence and alterations in circadian activity, neither of which were exacerbated by co-treatment with Δ 9 -THC. Combination treatment of oxycodone and Δ 9 -THC produced CPP when co-administered at doses that did not produce preference when administered alone. These data indicate that Δ 9 -THC may facilitate oxycodone-induced antinociception without augmenting certain unwanted features of opioid intake (e.g. dependence, circadian rhythm alterations). However, our findings also indicate that Δ 9 -THC may facilitate rewarding properties of oxycodone at therapeutically relevant doses which warrant consideration when evaluating this combination for its potential therapeutic utility. |
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| معلومات مُعتمدة: | F32 DA051160 United States DA NIDA NIH HHS; R01 DA049924 United States DA NIDA NIH HHS; R01 DA058755 United States DA NIDA NIH HHS; R34 NS126036 United States NS NINDS NIH HHS |
| تواريخ الأحداث: | Date Created: 20231218 Latest Revision: 20231225 |
| رمز التحديث: | 20231225 |
| مُعرف محوري في PubMed: | PMC10723318 |
| DOI: | 10.1101/2023.12.04.569809 |
| PMID: | 38105953 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.12.04.569809 |
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