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. <i>Scube1</i> (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 <i>Scube1</i> 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; <i>H3b</i> 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 <i>Scube1</i> expression (2^-ΔCq, hemispheres averaged when available) and perseverative errors (average over reversals 1-3). Exploratory correlations were run for <i>Wdr7, Chd8,</i> and <i>Sapap3</i> (α=0.05). Results Primer evaluation yielded four acceptable targets (<i>Scube1, Wdr7, Chd8, Sapap3</i>). <i>Scube1</i> expression in DMS positively correlated with perseveration (r(39)=0.35; p=0.027). No significant associations were observed for <i>Wdr7</i> (r(39)=0.16; p=0.32), <i>Chd8</i> (r(39)=0.11, p=0.46), or <i>Sapap3</i> (r(39)=0.18; p=0.27). Conclusions Higher <i>Scube1</i> 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.