Oxytocin and Dopamine Receptor Expression: Cellular Level Implications for Pair Bonding

Oxytocin ( Oxtr ) and dopamine ( Drd1 , Drd2 ) receptors provide a canonical example for how differences in neuromodulatory receptors drive individual and species-level behavioral variation. These systems exhibit striking and functionally-relevant differences in nucleus accumbens (NAc) expression across monogamous prairie voles ( Microtus ochrogaster ) and promiscuous meadow voles ( Microtus pennsylvanicus ). However, their cellular organization remains largely unknown. Using multiplex in situ hybridization, we mapped Oxtr , Drd1 , and Drd2 expression in sexually naïve and mate-paired prairie and meadow voles. Prairie voles have more Oxtr+ cells than meadow voles, but Oxtr distribution across dopamine-receptor cell class was similar, indicating a general upregulation rather than cell class bias. Oxtr was enriched in cells that express both dopamine receptors ( Drd1+/Drd2+ ) in prairie voles, suggesting these cells may be particularly sensitive to oxytocin. We found no species or pairing-induced differences in Drd1+ or Drd2+ cell counts, suggesting prior reports of expression differences may reflect upregulation in cells already expressing these receptors. Finally, we used single-nucleus sequencing to provide the first comprehensive map of Oxtr and Drd1-5 across molecularly-defined NAc cell types in the prairie vole. These results provide a critical framework for understanding how nonapeptide and catecholamine systems may recruit distinct NAc cell types to shape social behavior.