Within- and Between-Subject Analyses of the Effects of Chronic Xylazine on Negative Phototaxis in Two Planarian Species

Xylazine, an adulterant found frequently in illicit fentanyl, has been implicated in causing several adverse effects in human recreational users, including skin lesions and complications in the treatment of opiate overdose. Despite these public health concerns, the literature on the basic behavioral effects of xylazine is limited. Recent research has demonstrated that planarians show potential as an emerging and practical animal model for studying the behavioral effects of acute xylazine exposure. The goal of the current investigation was to evaluate the behavioral effects of chronic xylazine administration on negative phototaxis in two planarian species: Girardia tigrina and Schmidtea mediterranea. Three experiments were conducted. Overall, 10 µM of chronic xylazine exposure, arranged according to a multiple-baseline design, impaired negative phototaxis in S. mediterranea but not G. tigrina. An ABA reversal design indicated that behavioral effects in S. mediterranea abated when chronic xylazine was terminated. Finally, a between-group design replicated potential interspecies differences when G. tigrina and S. mediterranea were compared directly, with the latter showing significantly greater susceptibility to drug effects. This work provides evidence of the utility of a planarian model for studying the behavioral effects of xylazine and lays the foundation for further investigation into the chronic effects of the drug.