Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms.

Psilocybin is a serotonergic 5-HT2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [5-HT]) system. We quantified stereotyped movements (e.g. head bops, twists, scrunches, and C-shapes) and defensive responding (negative phototaxis) and probed a 5-HT2A R mechanism for psilocybin using a selective 5-HT2A R antagonist (volinanserin). Psilocybin (0.01, 0.1, 1, and 10 nM) increased all stereotyped movements and, at higher concentrations, reduced motility. Volinanserin (1, 10, and 100 nM) did not induce any stereotyped movements or reduce motility. For combination experiments, volinanserin reduced cumulative stereotyped movements produced by psilocybin (0.01 nM) and specifically reduced psilocybin-evoked twists and head bops. Concentrations (