Blocking IL-17A prevents oxycodone-induced depression-like effects and elevation of IL-6 levels in the ventral tegmental area and reduces oxycodone-derived physical dependence in rats
Copyright © 2024 Elsevier Inc. All rights reserved..
Oxycodone is the most prescribed opioid for pain management and has been available in clinics for almost a century, but effects of chronic oxycodone have been studied less than morphine in preclinical and clinical studies. Newly developed depression has been coupled with chronic oxycodone use in a few clinical studies, but no preclinical studies have investigated the pathogenesis of oxycodone-induced depression. Gut microbiome changes following oxycodone use is an understudied area, and interleukin-17A (IL-17A) is linked to both the development of mood disorders and regulation of gut microbiome. The present study investigated effects of chronic oxycodone exposure on mood-related behaviors (depression and anxiety), pain hypersensitivity, physical dependence, immune markers, and the gut microbiome and tested the hypothesis that blocking IL-17A with a systemically administered monoclonal antibody reduces oxycodone-derived effects. Oxycodone (using an incremental dosing regimen) or saline was injected twice a day for 12 days. IL-17A Ab (200 µg/100 µl) or saline was administered every 3rd day during the 12-day interval. Chronic oxycodone induced a depression-like effect, but not anxiogenic- or anxiolytic-like effects; promoted hyperalgesia; increased IL-17A and IL-6 levels in the ventral tegmental area (VTA); and induced physical dependence. IL-17A Ab co-administration with oxycodone prevented the depression-like effect and hyperalgesia, reduced naloxone-precipitated withdrawal signs, and normalized the increase in cytokine levels. Chronic oxycodone exposure did not affect gut microbiome and integrity. Our results identify a role for IL-17A in oxycodone-related behavioral and neuroimmune effects and show that IL-17A Ab has potential therapeutic value in blocking these effects. Given that humanized IL-17A Ab is approved for treatment of psoriasis and psoriatic arthritis, our findings point toward studying it for use in the treatment of oxycodone use disorder.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
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| Enthalten in: |
Brain, behavior, and immunity - 117(2024) vom: 01. März, Seite 100-111 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Inan, Saadet [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2024.01.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366901052 |
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| 245 | 1 | 0 | |a Blocking IL-17A prevents oxycodone-induced depression-like effects and elevation of IL-6 levels in the ventral tegmental area and reduces oxycodone-derived physical dependence in rats |
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| 520 | |a Oxycodone is the most prescribed opioid for pain management and has been available in clinics for almost a century, but effects of chronic oxycodone have been studied less than morphine in preclinical and clinical studies. Newly developed depression has been coupled with chronic oxycodone use in a few clinical studies, but no preclinical studies have investigated the pathogenesis of oxycodone-induced depression. Gut microbiome changes following oxycodone use is an understudied area, and interleukin-17A (IL-17A) is linked to both the development of mood disorders and regulation of gut microbiome. The present study investigated effects of chronic oxycodone exposure on mood-related behaviors (depression and anxiety), pain hypersensitivity, physical dependence, immune markers, and the gut microbiome and tested the hypothesis that blocking IL-17A with a systemically administered monoclonal antibody reduces oxycodone-derived effects. Oxycodone (using an incremental dosing regimen) or saline was injected twice a day for 12 days. IL-17A Ab (200 µg/100 µl) or saline was administered every 3rd day during the 12-day interval. Chronic oxycodone induced a depression-like effect, but not anxiogenic- or anxiolytic-like effects; promoted hyperalgesia; increased IL-17A and IL-6 levels in the ventral tegmental area (VTA); and induced physical dependence. IL-17A Ab co-administration with oxycodone prevented the depression-like effect and hyperalgesia, reduced naloxone-precipitated withdrawal signs, and normalized the increase in cytokine levels. Chronic oxycodone exposure did not affect gut microbiome and integrity. Our results identify a role for IL-17A in oxycodone-related behavioral and neuroimmune effects and show that IL-17A Ab has potential therapeutic value in blocking these effects. Given that humanized IL-17A Ab is approved for treatment of psoriasis and psoriatic arthritis, our findings point toward studying it for use in the treatment of oxycodone use disorder | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Anxiety | |
| 650 | 4 | |a Dependence | |
| 650 | 4 | |a Depression | |
| 650 | 4 | |a Gut microbiome | |
| 650 | 4 | |a Hyperalgesia | |
| 650 | 4 | |a IL-17A | |
| 650 | 4 | |a IL-17A Ab | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a Oxycodone | |
| 650 | 7 | |a Oxycodone |2 NLM | |
| 650 | 7 | |a CD35PMG570 |2 NLM | |
| 650 | 7 | |a Interleukin-17 |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 700 | 1 | |a Meissler, Joseph J |e verfasserin |4 aut | |
| 700 | 1 | |a Bessho, Shingo |e verfasserin |4 aut | |
| 700 | 1 | |a Wiah, Sonita |e verfasserin |4 aut | |
| 700 | 1 | |a Tukel, Cagla |e verfasserin |4 aut | |
| 700 | 1 | |a Eisenstein, Toby K |e verfasserin |4 aut | |
| 700 | 1 | |a Rawls, Scott M |e verfasserin |4 aut | |
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