MODULATION OF NEURAL PLASTICITY AND CONTEXTUAL FEAR CONDITIONING AND EXTINCTION BY A <EM>PSILOCYBE CUBENSIS</EM> EXTRACT IN HIGH- AND LOW-FREEZING WISTAR RAT LINES

Psilocybin is under investigation for its sustained neuroplasticity-promoting effects. Here, we assessed the impact of a Psilocybe cubensis alkaloid extract on contextual fear conditioning and extinction in Wistar Carioca rats with high (CAC) or low (CBC) freezing phenotypes and in a control line (CTR). A single psilocybin dose (1 mg/kg, i.p.) was administered 24 h before or after conditioning, and neural plasticity was evaluated in the infralimbic prefrontal cortex (CPF) and hippocampus (HIP) via BDNF Western blotting, with Sholl-based morphological analyses in progress. When administered before conditioning, psilocybin induced an anxiogenic-like increase in freezing in CAC rats before conditioning (p = 0.0295) and in CTR rats after conditioning (p = 0.0074), while producing an anxiolytic-like reduction in freezing during conditioning in CBC rats (p = 0.0037). Post-conditioning psilocybin reduced fear extinction rates in CTR males during the first extinction session (p = 0.0483) and, after completion of all extinction phases, in CAC males (p = 0.0146). At the molecular level, psilocybin significantly modulated BDNF expression, increasing its levels in CAC rats in both the CPF (p = 0.0075) and HIP (p = 0.0028), and in the HIP of CTR rats (p = 0.0114), with large effect sizes. No significant treatment-related effects were detected in CBC rats or in the CPF of CTR animals (p > 0.20). Overall, these findings demonstrate that psilocybin-induced psychoplastogenic effects are strongly modulated by genetic background, brain region and the timing of administration, highlighting that individual behavioral traits critically shape both behavioral and molecular outcomes.