Correlation of repetitive behaviors in deer mice with striatal mRNA expression of endogenous opioids and mu, delta, kappa, and dopamine receptors.

Deer mice provide a valuable naturally occurring animal model for investigating pathophysiological mechanisms underlying repetitive behaviors. Prior investigations using this model have identified abnormalities in the cortico-basal ganglia circuitry, including alterations within the indirect pathway and levels of endogenous opioids in the frontal cortex. In this study, the behaviors of n = 7 mice were quantified, and their brains were sectioned. Using analysis of in-situ mRNA hybridization (RNAscope®) in four striatal regions (dorsomedial, dorsolateral, ventromedial and ventrolateral), mRNA levels of dopamine receptors (DRD-1 [D1] and DRD-2 [D2]), endogenous opioids (prodynorphin [p-dyn] and proenkephalin [p-enk]), and opioid receptor expression (Oprm1 [mu], Oprd1 [delta], Oprk1 [kappa]) were quantified. Statistical analyses were performed using Spearman's rank correlation coefficients with a False Discovery Rate (FDR) procedure to address the small sample size. Results identified a positive correlation between total activity and DRD-2 mRNA in the dorsolateral striatum. The discussion reviews the potential effect of dopaminergic alterations on several cortical-basal ganglia-thalamo-cortical pathways, the possible role of other brain regions and neurotransmitters, and suggestions for future investigative approaches.