Title: Anxiety-like Behaviors in Juvenile SAPAP3-KO Mice: A Model for Obsessive-Compulsive Disorder

Summary: Juvenile SAPAP3-knockout (SAPAP3-KO) mice exhibit anxiety-like behaviors before developing excessive self-grooming, a model for obsessive-compulsive disorder (OCD). These behaviors did not respond to psilocybin treatment, and changes in synaptic proteins were observed in adult SAPAP3-KO mice.

Body:
Background:
Obsessive-compulsive disorder (OCD) often originates in adolescence and is usually preceded by anxiety. To understand the developmental trajectory of OCD and its neurobiological underpinnings, the study used SAPAP3-knockout (SAPAP3-KO) mice, which develop excessive self-grooming behavior at 4-6 months of age, mirroring OCD symptoms.

Methods:
Two sets of experiments were conducted on juvenile (10-13 weeks) SAPAP3-KO mice, both male and female. The first experiment compared behavioral phenotypes between homozygous (HOM), heterozygous, and wild-type (WT) mice. The second evaluated a different sample of HOM and WT mice and assessed the effect of psilocybin (PSIL) treatment on the identified behavioral differences. Behavioral tests assessed anxiety-like behavior, social interaction, and cognitive function. The levels of four synaptic proteins, known to interact with SAPAP3, were also measured in the frontal cortex, hippocampus, amygdala, and striatum.

Results:
In both studies, juvenile HOM SAPAP3-KO mice exhibited significant anxiety-like behaviors compared to WT mice. This included spending less time in open field center and elevated plus maze open arms, burying fewer marbles, and finding fewer buried Oreos. Psilocybin treatment did not alleviate these behaviors. In adult male HOM mice, there were significant increases in three synaptic proteins across multiple brain regions, and in the frontal cortex of HOM females. These changes were not observed in juvenile mice.

Interpretation:
These results suggest that juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the characteristic self-grooming behavior of OCD. Psilocybin treatment, however, was ineffective in alleviating these symptoms. The observed increase in synaptic proteins in adult mice, but not juveniles, could represent compensatory plasticity changes associated with OCD-like behaviors.

Research Context:
This study was conducted by academic researchers studying the neurobiological underpinnings of OCD. Their work contributes to our understanding of the developmental trajectory of OCD-like behaviors and possible neuroplastic adaptations.