• Farhan Augustine, Shawn M Doss, Justin Pellicciotti, Sahar Mahate, and Harvey S Singer.
• Johns Hopkins University School of Medicine, Department of Neurology, and the Kennedy Krieger Institute, Baltimore, MD, USA; University of Maryland Baltimore County, Department of Biological Sciences, Baltimore, MD, USA.
• Neuroscience. 2025 Jan 3; 568: 324332324-332.

AbstractRepetitive motor behaviors are common in both neurotypical and developmentally delayed populations. The neural mechanisms underlying these behaviors are not fully understood, but cortical-basal ganglia-thalamo-cortical (CBGTC) circuitry is often implicated. Peromyscus maniculatus bairdii (deer mice), which exhibit spontaneous repetitive actions analogous to human motor stereotypies and obsessive-compulsive behaviors, serve as an effective model for studying repetitive behaviors. This preliminary study investigates the relationship between repetitive motor activity and striatal expression of endogenous opioids and dopamine receptors in deer mice. Behavioral assessment involved video-confirmed quantification of leaping, hopping, and rearing in seven mice. Using in-situ mRNA hybridization (RNAscope®), we quantified mRNA levels of proenkephalin, prodynorphin, mu, delta, and kappa opioid receptors, and D1 and D2 dopamine receptors in four striatal sub-regions: dorsomedial (DMS), dorsolateral (DLS), ventromedial (VMS), and ventrolateral (VLS). Associations between mRNA fluorescence and behavioral activity were evaluated using Spearman's rank correlations adjusted for false discovery rate (FDR). Results showed a significant positive correlation between D2 dopamine receptor (DRD2) mRNA expression in the DLS and total repetitive activity (p < 0.001). Additional positive DRD2 correlations in other regions did not reach significance after FDR adjustment. No significant relationships were found for DRD1 or endogenous opioid markers. These findings suggest that DRD2 expression in the DLS may modulate repetitive behaviors in deer mice, highlighting the role of dopaminergic pathways within CBGTC circuitry. However, limitations such as small sample size and lack of protein-level verification require further investigation. Future research should explore translational implications of DRD2 modulation and analyze additional brain regions.Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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