ArticlePsychopharmacology2026
Xylazine potentiates the interoceptive effects of fentanyl in male and female rats.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The need to incorporate polysubstance use in neuropsychopharmacology research: Biological lessons and new opportunities.Addiction neuroscience · 2026Article
- Reinforcing effects of fentanyl/xylazine mixtures in monkeys responding under a food-versus-drug choice procedure.Behavioural pharmacology · 2026Article
- The opioid flexion phenotype: postural flexion and nodding in the fentanyl era.Frontiers in neuroscience · 2026Article
- Within- and Between-Subject Analyses of the Effects of Chronic Xylazine on Negative Phototaxis in Two Planarian Species.Biomolecules · 2025Article
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Abstract
rationaleXylazine, a sedative typically used in veterinary medicine, has been increasingly detected as an adulterant in the unregulated opioid supply and present in opioid overdose deaths. Therefore, xylazine-adulterated fentanyl is a growing public health concern. People who use drugs have reported that xylazine changes and prolongs the effects of fentanyl.
objectivesWe used standard operant drug discrimination procedures to better understand how xylazine impacts the discriminative stimulus/interoceptive effects of fentanyl.
methodsMale and female Long-Evans rats (n = 23) were trained to discriminate fentanyl (0.032 mg/kg intraperitoneal) such that one lever was reinforced with sucrose on days when fentanyl was administered, and the other lever was reinforced when vehicle was administered. Once rats met testing criteria, we tested a dose range of fentanyl to confirm discriminative stimulus control, then we tested if xylazine alone produced fentanyl-like effects and if the addition of xylazine to fentanyl impacted fentanyl interoceptive effects.
resultsStimulus control was confirmed, as rats showed increased percent responses on the fentanyl-appropriate lever as well as decreased response rates for increasing doses of fentanyl. Xylazine alone did not substitute for the stimulus effects of fentanyl but produced similar response rate reductions as fentanyl alone. Xylazine co-administered with fentanyl potentiated the stimulus effects of lower doses of fentanyl in both males and females and potentiated response rate reductions.
conclusionsThese results indicate that xylazine enhances the interoceptive effects of fentanyl, which may inform clinical research about xylazine-adulterated fentanyl.
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