Effects of Single-Dose Psilocybin on Whisker-Dependent Texture Discrimination Following Early Postnatal Whisker Trimming

Abstract

Psilocybin, a psychedelic compound, has recently been shown to have the potential to reopen critical periods—windows during development when neuroplasticity is heightened and the brain is especially receptive to acquiring specific skills. This property positions psilocybin as a promising therapeutic tool for promoting plasticity and facilitating rapid learning even in adulthood. In this study, we further explore this potential by administering psilocybin to mice subjected to whisker trimming at various postnatal ages. Early postnatal whisker trimming leads to tactile deficits, such as a poor ability to discriminate between different textures, since vibrissae play a critical role in allowing mice to interact with their environments. After whisker regrowth, we assessed texture discrimination abilities under psilocybin or saline conditions. Therefore, this study also provides the first detailed characterization of whisker growth and regrowth trajectories following trimming in mice. By trimming at five different postnatal ages, we aimed to identify a critical period for texture discrimination, and to determine whether a single dose of psilocybin could promote recovery of later tactile function following disruption during this sensitive window. Our results show trends that suggest psilocybin may enhance recovery of texture discrimination in an age-dependent, non-linear manner. Mice trimmed at different postnatal ages and treated with psilocybin in adulthood showed variable recovery: minimal following postnatal day 0 (P0) trimming, maximal following P15 trimming, and reduced again following P20 trimming. The peak observed for P15 trimming coincides with a known period of dendritic remodeling and synaptic refinement in the barrel cortex, the primary somatosensory area for whisker input in rodents, suggesting that psilocybin reactivates plasticity mechanisms aligned with this developmental window.