Dissertation
INVESTIGATION OF THE EFFECTS OF HYPERBARIC OXYGEN (HBO2) ON OPIOID WITHDRAWAL USING BOTH BEHAVIORAL AND MOLECULAR TECHNIQUES
Doctor of Philosophy (PhD), Washington State University
01/2020
Handle:
https://hdl.handle.net/2376/111768
Abstract
Opioid dependence is likely impacted by repeated withdrawal cycles leading to the association of drug taking with relief of withdrawal symptoms which can include increased sensitivity to painful stimuli (hyperalgesia). Hyperbaric oxygen (HBO2) is approved to treat several conditions in humans and has shown potential in relieving both pain and opioid withdrawal. While HBO2 has shown potential in decreasing the severity of precipitated withdrawal in terms of somatic symptoms, it is not known how the treatment would impact spontaneous withdrawal. Not much is known of the neuroimmune interactions of spontaneous withdrawal in both sexes and how HBO2 might impact these potential endpoints. Therefore, the goals of this dissertation are to 1) conduct an investigation into the time course of withdrawal in terms of somatic symptoms and hyperalgesia in male and female NIH Swiss mice; 2) determine the effect of treatment with HBO2 on withdrawal and hyperalgesia in mice over this time course; and 3) determine the impact of morphine withdrawal and HBO2 on inflammatory cytokines and pathways. Female and male NIH Swiss mice were made dependent upon morphine using the same escalating dosing schedule in all experiments. Withdrawal was observed over 30-minute periods at regular time points and paw pressure measurements were taken after observations. Compared to their male counterparts, females showed more tremors, higher global withdrawal scores, and hyperalgesia that, while being equal in severity, returned to control levels faster. Jumps were not found to be a reliable indicator of withdrawal. A single treatment of HBO2 was found to prevent hyperalgesia in males and reduce it in females. This treatment did increase somatic withdrawal scores in males as well as inhibit weight gain during withdrawal. Multiple treatments of HBO2 at lower pressures prevented the development of hyperalgesia and caused an antinociceptive effect in female but not male mice. Global withdrawal scores were significantly reduced in mice after multiple low-pressure treatments and body weight change was unaffected in female mice. Morphine withdrawal decreased levels of IL-6, TNF-α, IL-1β in female mice and reduced TLR4 levels in both sexes depending upon brain section. HBO2 had no significant impact on cytokine levels.
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Details
- Title
- INVESTIGATION OF THE EFFECTS OF HYPERBARIC OXYGEN (HBO2) ON OPIOID WITHDRAWAL USING BOTH BEHAVIORAL AND MOLECULAR TECHNIQUES
- Creators
- Abigail Lucille Brewer
- Contributors
- Raymond M Quock (Advisor)Rebecca M Craft (Committee Member)Michael M Morgan (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Psychology, Department of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 114
- Identifiers
- 99900581811101842
- Language
- English
- Resource Type
- Dissertation