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Abstract
Background: Opioids are a class of drugs that are utilized in clinical settings to alleviate acute and chronic pain, but can often lead to development of tolerance, addiction and overdose following prolonged usage. Opioids such as morphine function by activating endogenous µ opioid receptors, which are located in various tissues throughout the body. Astrocyte Elevated Gene-1 (AEG-1) is a multifunctional protein that regulates inflammation, myeloid cell activity and lipid metabolism. Studies have shown interactions and overlaps in cellular signaling between the inflammatory/immune responses and the endogenous opioid system which could suggest a role for AEG-1 in opioids effects. Our goal is to investigate the role of AEG-1 in morphine mediated pharmacological effects including analgesia. Methods: Adult AEG-1 global knockout (KO) and wild-type (WT) male and female mice (C57BL/6J background) were utilized to assess morphine-induced thermal antinociception (The tail immersion assay test), hyperlocomotion, gastrointestinal (GI) transit inhibition, and tolerance. GI transit was assessed via charcoal transit assay. Locomotor boxes were used to assess spontaneous activity in mice. Results: AEG-1 KO mice displayed increased thermal antinociception following acute and repeated morphine administration compared to their WT counterparts. Pretreatment with naloxone blocked the enhancement of morphine thermal antinociception in AEG-1 KO mice. In addition, chronic morphine treated AEG-1 KO mice displayed reduced morphine tolerance development compared to their WT counterparts. No significant differences in morphine-induced hyperlocomotion or GI transit inhibition were observed between AEG-1 KO and WT mice. Conclusions: Our data suggest that AEG-1 deletion enhances the antinociceptive effects of morphine and reduces tolerance to chronic morphine treatment. However, AEG-1 deletion does not impact morphine-induced locomotor activity of GI transit inhibition. Overall, our results suggest that AEG-1 may function as a modulator of the endogenous opioid system.
Publication Date
2022
Subject Major(s)
Biology, Chemistry
Keywords
Morphine, Opioids, Astrocyte Elevated Gene-1, Chronic Treatment, Naloxone, GI Transit, Locomotor Assay
Disciplines
Life Sciences | Medicine and Health Sciences
Current Academic Year
Senior
Faculty Advisor/Mentor
M. Imad Damaj, Ph.D.
Rights
© The Author(s)