# Dorsomedial Striatal Scube1 Expression Correlates With Perseveration in a Rat Reversal-Learning Task

## TL;DR

Higher expression of the Scube1 gene in the rat dorsomedial striatum is linked to increased perseveration during reversal learning, suggesting a possible role in cognitive inflexibility seen in OCD.

## Contribution

This study identifies a novel correlation between Scube1 gene expression in the dorsomedial striatum and perseverative behavior in rats during reversal learning.

## Key findings

- Scube1 expression in the dorsomedial striatum positively correlates with perseverative errors during reversal learning.
- No significant correlations were found for Wdr7, Chd8, or Sapap3 gene expressions with perseveration.
- The study suggests a potential role for vascular/inflammatory pathways in cognitive inflexibility related to OCD.

## Abstract

Background

Obsessive-compulsive disorder (OCD) is associated with reversal-learning deficits and dysregulation within cortico-striatal circuitry. Genetic studies have nominated several OCD risk genes, but their relationship to striatal gene expression and cognitive inflexibility in vivo remains unclear. Scube1 (signal peptide, CUB, EGF-like domain-containing 1) is a secreted EGF-related glycoprotein linked to vascular/inflammatory signaling; its relevance to DMS mechanisms of behavioral flexibility is unknown. This study aimed to test whether dorsomedial striatum (DMS) expression of candidate OCD genes (with Scube1 as the primary gene of focus) correlates with perseverative responding during reversal learning in rats.

Methods

Male Lister-hooded rats previously trained on a serial two-hole spatial discrimination with within-session reversals were used. After the final session, DMS tissue was micropunched for SYBR-green, real-time polymerase chain reaction (RT-qPCR). Primers were designed by Primer-BLAST and screened by melt-curve QC; H3b served as the reference gene (cyclophilin cross-check). Expression for all targets was 2−ΔCq (H3b-normalised; hemispheres averaged when available). The pre-specified primary endpoint was the correlation between Scube1 expression (2−ΔCq, hemispheres averaged when available) and perseverative errors (average over reversals 1-3). Exploratory correlations were run for Wdr7, Chd8, and Sapap3 (α=0.05).

Results

Primer evaluation yielded four acceptable targets (Scube1, Wdr7, Chd8, Sapap3). Scube1 expression in DMS positively correlated with perseveration (r(39)=0.35; p=0.027). No significant associations were observed for Wdr7 (r(39)=0.16; p=0.32), Chd8 (r(39)=0.11, p=0.46), or Sapap3 (r(39)=0.18; p=0.27).

Conclusions

Higher Scube1 expression in rat DMS is associated with greater perseverative responding, suggesting a vascular/inflammatory-linked pathway may contribute to cognitive inflexibility relevant to OCD. Findings support using risk-gene-guided targets in animal models to probe OCD pathophysiology. Replication with full qPCR efficiency calibration and prospective power analysis is warranted.