Date of Award
5-2026
Document Type
Thesis
Degree Name
Master of Arts in Psychological Science
Department
Psychology
First Reader/Committee Chair
Cynthia Crawford
Abstract
The growing prevalence of fentanyl adulterated with xylazine presents a major public health concern, yet the behavioral and physiological effects of this combination remain poorly characterized. This study examined the effects of acute fentanyl administration, alone and in combination with xylazine, on opioid-induced hyperalgesia, affective behavior, and mortality in male and female Sprague-Dawley rats (n=80). Rats received four fentanyl injections (60 µg/kg) administered at 15-minute intervals, with or without xylazine (0, 0.1, 0.333, or 1.0 mg/kg), as well as a saline control condition. Pain sensitivity was assessed using a hot plate assay at 6.5, 12, 24, and 48 hours post-injection. Depressive-like behavior was measured via sucrose preference, and anxiety-like behavior was assessed using the light/dark box test. Morphine-induced antinociception and mortality were also evaluated. Our hypothesis was that the acute addition of xylazine would alter nociception sensitivity, heighten anxiety and depressive-like behaviors.
Contrary to predictions, fentanyl did not produce significant hyperalgesia, and xylazine did not increase pain sensitivity at any dose. No significant effects of drug treatment or sex were observed in sucrose preference, indicating no evidence of anhedonia following acute exposure. In contrast, anxiety-like behavior showed sex-dependent effects: fentanyl alone increased anxiety-like responding, particularly in females, whereas some fentanyl–xylazine combinations appeared to attenuate these effects in males. Mortality analyses indicated higher lethality in the fentanyl-only group, especially in males; co-administration of xylazine did not increase mortality.
Together, these findings suggest that acute fentanyl–xylazine exposure does not exacerbate hyperalgesia or depressive-like behavior and may mitigate select anxiety-related effects. Future studies should evaluate a broader range of xylazine doses and incorporate repeated-exposure designs to clarify how dose and exposure history shape fentanyl–xylazine interactions.
Recommended Citation
Lujan, Alejandra R., "Investigating Fentanyl-Xylazine Interactions: Implications for Opioid-Induced Hyperalgesia and Affective Dysregulation in Rats" (2026). Electronic Theses, Projects, and Dissertations. 2451.
https://scholarworks.lib.csusb.edu/etd/2451