Psychedelics research in rodents has a behavior problem

Rodent behavioral research on psychedelics faces a “behavior problem” because commonly used, simple drug-screening assays do not reliably reveal psychedelic mechanisms that translate to people. A multisite effort across five labs tested around 200 mice given psilocybin and measured performance across standard tasks like the elevated plus maze, open field, tail suspension, and forced swim. The mice showed a temporary increase in anxiety-like behaviors while on the drug, but the effects did not persist after it wore off, highlighting inconsistencies when trying to map rodent behavior to human outcomes. Researchers argue the issue is not only between-lab replication, but that many assays were validated for pharmacology screening and are too blunt, too “one-shot,” or too sensitive to small environmental and handling differences. Alternative approaches use more theory-driven, computationally modelable decision-making tasks that can isolate processes relevant to negative affective bias or hallucination-like events, aiming to link specific neural mechanisms to psychedelic effects.