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Microglia and key pro-inflammatory cytokines mount weakened responses to immune challenge following abstinence from chronic fentanyl self-administration
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Dao, Angela. Microglia and key pro-inflammatory cytokines mount weakened responses to immune challenge following abstinence from chronic fentanyl self-administration. Retrieved from https://doi.org/doi:10.7282/t3-eg4n-4y17

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TitleMicroglia and key pro-inflammatory cytokines mount weakened responses to immune challenge following abstinence from chronic fentanyl self-administration
NameDao, Angela (author); West, Mark (chair); Kusnecov, Alexander W (member); Barker, David J (member); Manvich, Daniel (member); Rutgers University; School of Graduate Studies
Date Created2022
Other Date2022-10 (degree)
SubjectPhysiological psychology, Neurosciences, Behavioral psychology, Addiction, Cytokines, Fentanyl, Microglia, Opioids, Self-administration
Extent1 online resource (59 pages) : illustrations
DescriptionSignificant evidence indicates immunomodulatory effects of opioids, but there is an absence of research on how neuroinflammatory events involving microglial activation are affected by chronic fentanyl self-administration (SA) or persist after cessation of drug. To test this, a rat model of voluntary chronic, long-access fentanyl SA was used to examine the pro-inflammatory cytokine and microglial response to chronic fentanyl abuse after abstinence from drug. Male Sprague-Dawley rats self-administered fentanyl (Fent/SA) for 30 consecutive days before being randomly assigned an abstinence period of either 1 week (N=8) or 1 month (N=6). Control animals (Sal/SA) similarly received access to SA saline and subsequent abstinence periods (N=12). On the last day of abstinence, all animals received an injection of an inflammatory stimulus (lipopolysaccharide; 1.5 mg/kg, i.p.), followed by perfusion and collection of spleen and brain. Sandwich enzyme-linked immunosorbent assays (ELISAs) were conducted to analyze concentrations of IL-1β and IL-6, and all brains underwent immunohistochemistry for the microglial marker Iba1 to quantify microglial cell numbers and analyze morphological states. Soma area, soma circularity, and number of branches were measured and combined to generate an individual activation score of microglial cells. We observed suppression of LPS-induced IL-6 in Fent/SA animals at 1 week of abstinence compared to Sal/SA animals, that recovered after 1 month of abstinence; no change was observed in IL-1β concentrations. Additionally, at 1 week of abstinence Fent/SA animals exhibited greater microglial density, but decreased LPS-induced activation, compared to Sal/SA; after 1 month of abstinence, decreased activation persisted but microglial density had decreased to be less than Sal/SA animals. These data indicate that chronic fentanyl use generates lasting suppression of microglial activity, showing for the first time that the neuromodulatory effects of fentanyl persist after extended abstinence from drug.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
Persistent URLhttps://doi.org/doi:10.7282/t3-eg4n-4y17
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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