Cellular and Molecular NeuroscienceResearch PaperDistribution of D1 and D5 dopamine receptors in the primate nucleus accumbens

The D1 family of dopamine receptors (D1R) play a critical role in modulating reward in the nucleus accumbens (NAc). A better understanding of how D1Rs modulate NAc function must take into account the contributions of the two D1R subtypes, D1 and D5. In order to determine how these two subtypes contribute to dopamine's actions in the NAc, we utilized subtype specific antibodies and immunoelectron microscopy to quantitatively determine the localization of D1 and D5 in the neuropil of the primate NAc. We found that D1 was more commonly found in dendritic shafts and spines, while D5 was more commonly found in axon terminals, preterminal axons and glial processes. However, D5 is well positioned to play an important role in postsynaptic modulation of inputs onto NAc medium spiny neurons. Approximately one third of spines contained D1 and one quarter contained D5, and as we have previously observed in the prefrontal cortex (PFC) and amygdala, these receptors overlapped extensively in dendritic spines. Similarly, we found overlap of the two D1R in axon terminals in the NAc; however, here D5 labeled the larger population of terminals and D1 was found in a subpopulation of D5 containing terminals. Given the higher affinity of D5 for dopamine, this suggest that presynaptic modulation of inputs by dopamine may be more easily evoked than in PFC where D1 is the dominate presynaptic receptor. Finally, we investigated differences between the NAc and the dorsal striatum. We found that in the caudate half of dendritic spines contain D1, significantly more than in the NAc. This suggests differences in how receptor is translated and distributed in D1 mRNA expressing medium spiny neurons in the NAc and caudate.