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199815 https://hdl.handle.net/2286/R.2.N.199815 http://rightsstatements.org/vocab/InC/1.0/ All Rights Reserved 2025 90 pages Masters Thesis Academic theses en Law, Olivia Marian Verpeut, Jessica Gewirtz, Jonathan Olive, M. Foster Arizona State University Partial requirement for: M.A., Arizona State University, 2025 Field of study: Psychology Opioid overdose deaths have risen a staggering degree in the last few decades. Crucially, during withdrawal from a drug, an individual experiences negative affective symptoms such as decreased sensitivity to reward (i.e., anhedonia) and accompanying neurobiological changes. Social behavior has also been implicated in addiction, but few rodent studies have used paradigms that model naturally occurring social behaviors. More research is needed to fully elucidate the mechanisms of these withdrawal states, as they may influence vulnerability for future drug use. The current study examined the effect of repeated oxycodone administration on spontaneous, 24hr withdrawal. Mice (n = 96) were injected with 5 mg/kg of oxycodone or saline vehicle for 10 days. First, a hot plate test was used to validate the dose of oxycodone in producing analgesia. Next, anhedonia was measured using the sucrose preference task. Then, a group open field paradigm in which 3 cage mates were allowed to freely interact was used to assess individual and social behavior, and the three-chamber task was used as an additional measure of sociability. Individual behavioral metrics in the open field and three-chamber were measured using Social LEAP Estimates Animal Poses (SLEAP). Lastly, tissue was collected during withdrawal and analyzed for c-Fos expression in reward-related regions or for gene markers of oligodendrocytes in the prefrontal cortex using quantitative polymerase chain reaction. The hot plate task demonstrated higher levels of thermal analgesia for all oxycodone doses at 15 minutes post-injection. Additionally, mice showed increased distance traveled in the open field 5 minutes post-oxycodone injection but not saline vehicle. Oxycodone-withdrawn mice did not show anhedonia in the sucrose preference test. In the open field task, oxycodone-withdrawn mice did not show differences in individual or group social behavior. Social preference also did not differ between control and oxycodone-withdrawn mice in the three-chamber task. Fluorescent immunohistochemistry analysis revealed similar c-Fos counts between groups in every region of interest. Finally, oligodendrocyte expression was similar between control and oxycodone-withdrawn animals. Overall, 5 mg/kg oxycodone-withdrawn mice did not show negative affective symptoms or neurobiological differences. Future studies aim to test different withdrawal timepoints and increased dosages of oxycodone. Psychology Neurosciences Biology Machine learning Oligodendrocytes Opioids Social Behavior Withdrawal Spontaneous Withdrawal in Mice Following Repeated Administration of a Low-Dose of Oxycodone