Psychedelic enhancement of flexible learning weeks after a single dose
bioRxiv – December 17, 2024
Source: medRxiv/bioRxiv/arXiv
Summary
A single dose of a specific psychedelic has been shown to enhance cognitive flexibility in mice, allowing them to adapt learned rules to new situations weeks later. This improvement aligns with structural changes in the brain's prefrontal cortex, highlighting the potential for psychedelics to support long-lasting learning and adaptability.
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.