Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats
Noah Cavallaro1 · Priya Rai1 · David Akins1 · Sima Soltanpour2 · Md Taufiq Nasseef3 · Richard J. Ortiz4 · Rachel Utama1 · Caitlyn R. Cody5 · Anoushka Mistry1 · Heather C. Brenhouse5 · Praveen P. Kulkarni1 · Craig F. Ferris1,6
1 Center for Translational Neuroimaging, Northeastern University, Boston, MA 02115, USA
2 School of Information Technology, Carleton University, Ottawa, ON K1S 5B6, Canada
3 Department of Mathematics, College of Science and Humanity Studies, Prince Sattam Bin Abdulaziz University, 16273 Riyadh, Saudi Arabia
4 Department of Psychology, Northern Illinois University, DeKalb, IL 60115, USA
5 Psychology Department, Northeastern University, Boston, MA 02115, USA
6 Departments of Psychology & Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA
Abstract
Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disconnection from forebrain structures. Paradoxically, resting-state analysis revealed global hyperconnectivity, with the cerebellum forming enhanced connections to the hippocampus, thalamus, somatosensory cortex, and midbrain. Mescaline abolished normal BOLD responses to rewarding olfactory stimuli, indicating disrupted sensory processing. Pre-pulse inhibition showed frequency-dependent acoustic gating effects: enhancement at 4 kHz (+ 27.6%) and 20 kHz (+ 27.3%), but impairment at 12 kHz (− 16.4%). These findings distinguish mescaline from LSD and psilocybin, implicating the cerebellum as a dysregulated sensory filter that floods forebrain circuits with unprocessed sensorimotor information—a potential mechanism underlying psychedelic-induced perceptual alterations.
Keywords
Hippocampus; Cerebellum; BOLD resting state functional connectivity; Pharmacological MRI; Reward; Fear
