Movie 4.

Xylazine-induced extrusion and tissue-wide contraction can be replicated with α2AR and OR agonists, respectively. Zebrafish larvae at 5 dpf were immobilized in a zWEDGI restraining device in E3 with 0.2 mg/mL and imaged following the addition of xylazine (5 mg/mL final), clonidine (5 mg/mL final), U-50488 (1 mM final), or an equal volume of water as a control. Note that keratinocyte extrusion and contraction are apparent in the xylazine-treated larvae, but only extrusion is apparent in clonidine-treated larvae. Further, U-50488 does not cause any significant extrusion but does cause considerable tissue contraction. Scale bars = 500 μm.

Evidence that xylazine disrupts skin homeostasis by acting on epithelial cells through the kappa opioid receptor

Tanner F. Robertson, Adam Horn, Frances M. Smith, and Anna Huttenlocher

Disease Models and Mechanisms 2026. 19:None-None; doi: 10.1242/dmm.052600