Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats

• DOI: 10.3389/fnins.2025.1554049
• Publication Date: 2025-05-01T04:14:57Z
• Authors: Evan Fuini; Arnold Chang; Richard J. Ortiz; Taufiq Nasseef; Josh Edwards; Marc Latta; Elias Gonzalez; Taylor J. Woodward; Bryce Axe; Ashwath Maheswari; Noah Cavallaro; Heather B. Bradshaw; Praveen P. Kulkarni; Craig F. Ferris
• Keywords: Psilocybin

Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This the first study to use MRI follow functional changes in brain activity response different doses of psilocybin fully awake, drug naive rats. We hypothesized that would show dose-dependent increase prefrontal cortex thalamus, while decreasing hippocampal activity. Female male rats were given IP injections vehicle or 0.03 mg/kg, 0.3 3.0 mg/kg awake during imaging session. These levels validated by measuring its metabolite, psilocin. Changes BOLD signal recorded over 20 min window. Data for resting state connectivity collected approximately 35 post injection. All data registered rat 3D atlas 169 areas providing site-specific global connectivity. Treatment resulted significant positive signal. The most affected acute presentation somatosensory cortex, basal ganglia thalamus. Males females showed sensitivity dose, exhibiting greater activation than males at especially thalamic regions. There was connectivity, highlighted hyperconnectivity cerebellum. Brain be involved loss sensory filtering organization motor stimuli, such as cortico-striato-thalamo-cortical circuit claustrum, increased higher psilocybin. Indeed, general neuroanatomical circuitry associated psychedelic experience but direction pattern between neural networks inconsistent human literature.