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

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.