Premorbid Characteristics of the SAPAP3-Mouse Model of Obsessive-Compulsive Disorder: Behavior, Neuroplasticity, and Psilocybin Treatment
bioRxiv – September 22, 2024
Source: medRxiv/bioRxiv/arXiv
Summary
SAPAP3-knockout mice, a model for obsessive-compulsive disorder, show signs of anxiety before developing compulsive grooming behaviors. This study explored their juvenile anxiety responses to psilocybin treatment and examined key proteins linked to brain plasticity. Remarkably, psilocybin reduced anxiety and promoted positive changes in neuroplasticity, highlighting its potential therapeutic benefits.
Abstract
Background SAPAP3-knockout (KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whether such behaviors respond to psilocybin treatment. The study also examined four key neuroplasticity-related synaptic proteins—GAP43, PSD95, synaptophysin, and SV2A — as SAPAP3 is a postsynaptic scaffold protein that interacts with PSD95 and may affect synaptic function.