Table 1_Acute psilocin increased cortical activity in rat.xlsx

Psilocin, a naturally occurring hallucinogenic component of magic mushrooms, exerts notable psychoactive effects in both humans and rodents. However, the underlying mechanisms remain not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a valuable tool in many preclinical and clinical trials for investigating changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocin on rats have not been thoroughly explored. This study aimed to explore the impact of psilocin on rats’ brain activity by combining BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocin hydrochloride injection (2.0 mg/kg, i.p.), elevated brain activity was detected in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. Moreover, a region-of-interest (ROI) -wise FC analysis matrix indicated enhanced interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex with the cortical and striatal areas. In addition to the fMRI observations, acute psilocin led to an increase in the EGR1 level in most cortical and striatal regions, indicating a consistent activation throughout the cortical and striatal areas. In conclusion, the psilocin-induced hyperactive state in rats is congruent to that in humans, and the increased brain activity, enhanced functional connectivity and up-regulation of EGR1 may be responsible for its pharmacological effects.