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bioRxiv · 10.1101/2024.12.17.629035

Psychedelic enhancement of flexible learning weeks after a single dose

Brouns, E. J.·Ekins, T. G.·Ahmed, O. J.
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Abstract

Psychedelic drugs have shown therapeutic potential for the treatment of multiple neuropsychiatric disorders chiefly by promoting long-lasting plasticity in the prefrontal cortex (PFC). A critical function of the PFC is the ability to apply previously learned rules to novel scenarios, a skill known as cognitive flexibility. Here, we show that a single dose of 25CN-NBOH - a serotonin 2A receptor-preferring psychedelic - improves performance on a relatively complex flexible reversal learning task in mice, measured 2-3 weeks after the dose. This effect was seen in both male and female mice. This behavioral finding complements previous cellular results showing that a single psychedelic dose induces long-term structural changes in the PFC and uniquely demonstrates sustained improvements in cognitive flexibility in a novel behavioral paradigm weeks after the initial psychedelic dose in mice. This high throughput task also provides a rapid, automated way to assess other candidate psychedelics for their impact on cognitive flexibility in mice.

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Brouns, E. J., Ekins, T. G., Ahmed, O. J.. 2024-12-20. Psychedelic enhancement of flexible learning weeks after a single dose. https://doi.org/10.1101/2024.12.17.629035

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