Serotonergic modulation of cortical gamma synchronization: right-lateralized psilocin effects on 40 Hz auditory steady-state responses in rats

Auditory steady-state responses (ASSRs), particularly at 40 Hz, are promising biomarkers for psychiatric disorders involving dysregulated neural synchronization. Although most ASSR studies have focused on the glutamatergic system, the serotonergic system, specifically 5-HT2A receptor signaling, has received limited attention. Psilocin, the active metabolite of psilocybin and a known 5-HT2A receptor agonist, alters cortical oscillatory activity, but its effects on ASSR dynamics remain unclear. In this study, we examined psilocin's effects on ASSRs in eight adult male Wistar rats implanted with 21 cortical electrodes. The rats were exposed to 40 Hz and 80 Hz click-train stimulation before and 30 min after subcutaneous psilocin administration (4 mg/kg). EEG signals were analyzed using time-frequency decomposition to extract phase-locking index (PLI) and event-related spectral perturbation (ERSP) values from frontal and temporal regions of both hemispheres. Psilocin selectively decreased PLI at 40 Hz stimulation in the right temporal cortex, with no significant changes in the frontal or left temporal regions, nor in response to 80 Hz stimulation. ERSP analysis revealed a global reduction in spectral power after psilocin administration in response to 80 Hz stimuli, but no consistent effects at 40 Hz. These results indicate that psilocin induces region- and frequency-specific alterations in auditory neural synchronization, characterized by right-lateralized disruption of 40 Hz phase-locking. This highlights the sensitivity of low-gamma oscillations to serotonergic modulation and supports the use of ASSR paradigms in translational models of altered perceptual and cognitive states.<b>NEW & NOTEWORTHY</b> This is the first preclinical study to demonstrate that psilocin selectively disrupts auditory steady-state responses (ASSRs) in rats in a frequency- and region-specific manner. The findings indicate a right-lateralized reduction in phase-locking at 40 Hz, along with a global suppression of spectral power at 80 Hz. These results provide new insights into the serotonergic modulation of neural synchrony and support the use of ASSRs as a translational biomarker for altered perceptual states.