Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice.
Autor: | Bedard ML; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Pharmacology, University North Carolina at Chapel Hill, Chapel Hill, NC, USA., Lord JS; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Perez PJ; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Bravo IM; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Teklezghi AT; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Tarantino L; Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC USA.; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Diering G; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., McElligott ZA; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Pharmacology, University North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. |
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Jazyk: | angličtina |
Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Feb 15. Date of Electronic Publication: 2023 Feb 15. |
DOI: | 10.1101/2022.04.06.487380 |
Abstrakt: | Opioid misuse has dramatically increased over the last few decades resulting in many people suffering from opioid use disorder (OUD). The prevalence of opioid overdose has been driven by the development of new synthetic opioids, increased availability of prescription opioids, and more recently, the COVID-19 pandemic. Coinciding with increases in exposure to opioids, the United States has also observed increases in multiple Narcan (naloxone) administrations as life-saving measures for respiratory depression, and, thus, consequently, naloxone-precipitated withdrawal. Sleep dysregulation is a main symptom of OUD and opioid withdrawal syndrome, and therefore, should be a key facet of animal models of OUD. Here we examine the effect of precipitated and spontaneous morphine withdrawal on sleep behaviors in C57BL/6J mice. We find that morphine administration and withdrawal dysregulate sleep, but not equally across morphine exposure paradigms. Furthermore, many environmental triggers promote relapse to drug-seeking/taking behavior, and the stress of disrupted sleep may fall into that category. We find that sleep deprivation dysregulates sleep in mice that had previous opioid withdrawal experience. Our data suggest that the 3-day precipitated withdrawal paradigm has the most profound effects on opioid-induced sleep dysregulation and further validates the construct of this model for opioid dependence and OUD. Highlights: Morphine withdrawal differentially dysregulates the sleep of male and female mice3-day precipitated withdrawal results in larger changes than spontaneous withdrawalOpioid withdrawal affects responses to future sleep deprivation differently between sexes. |
Databáze: | MEDLINE |
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