Evolutionary Divergence in Dopamine Regulation between Rodents and Primates and Its Implications for Neurobiological Research

Dopamine orchestrates essential functions such as sleep, movement, and learning, as well as shaping complex behaviors including reward motivation, decision-making, and social interaction. For this reason, many studies have been conducted to understand the role of dopamine in these processes. Often this work has performed using mice because of their availability and cost-effectiveness and because their brain structure and function are generally homologous to those of humans and nonhuman primates, particularly in midbrain–basal ganglia circuitry. Moreover, direct species comparisons have demonstrated similar dorsal-to-ventral gradients of dopamine release in the striatum of rodents and nonhuman primates (Cragg et al., 2000; Calipari et al., 2012), suggesting a conserved system for action selection and reward processing. Yet, species differences exist. For instance, comparative neuroanatomical studies showed that whereas in nonhuman primates, the caudate and putamen are two distinct nuclei; in mice these structures are fused into a single caudate putamen, or striatum, which is located beneath the cortex (Zeiss, 2005). Moreover, the organization of the mesocortical dopaminergic system is notably more complex in primates, with larger, more organized terminal fields, distinct neuropeptide colocalization, and earlier prenatal development (Berger et al., 1991). In light of these and other interspecies differences in dopaminergic pathway organization, Shin et al. (2025) recently compared dopamine release and its regulation in mice and macaques. They used two complementary methods to monitor dopamine release in dorsal striatum brain slices. The first method, fast-scan cyclic voltammetry (FSCV), allows quantification of electrically evoked dopamine release, but it has relatively low sensitivity and limited temporal resolution (10 Hz). To overcome these limitations, the authors used photometry, using the genetically encoded fluorescent dopamine sensors GRAB-DA1m and dLight1.3b. These sensors, in which GFP is fused to the intracellular loop 3 (ICL3) of the D1 receptors, respectively, allow real-time, … Correspondence should be addressed to Letizia Zanetti at lz3041{at}cumc.columbia.edu.