Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration.
Psychedelics April 22, 2025 Elizabeth J Brouns, Tyler G Ekins, Omar J Ahmed
A single dose of the selective serotonin 2A receptor agonist 25CN-NBOH produces long-lasting improvements in cognitive flexibility in both male and female mice, measured 2-3 weeks after treatment. In an automated sequential learning task, treated mice showed superior adaptability in rule reversal compared to controls, with better poke efficiency, higher correct trial percentages, and increased reward acquisition. These behavioral results extend prior cellular findings on psychedelic-induced structural remodeling in the prefrontal cortex and demonstrate sustained cognitive benefits weeks after a single dose. The automated task offers a high-throughput method for evaluating cognitive flexibility effects of psychedelic compounds, with implications for conditions like depression, PTSD, and Alzheimer's disease.