AbstractPrevious studies have shown significant changes in dopamine and opioid receptors in the basal ganglia following administration of cocaine. Cocaine administration results in a significant increase in the number of opioid receptors in dopamine‐enriched brain regions. The aim of this study was to determine if dopamine D2 receptors (D2r) and μ‐opioid receptors (μOr) are localized to the same neurons in the dorsolateral striatum. Immunoperoxidase and immunogold‐silver labeling combined with electron microscopy was used to examine the ultrastructural localization of both receptors in the dorsolateral striatum. Approximately half of the μOr‐labeled somatodendritic processes showed immunolabeling for the D2r. Similarly, about half of the D2r‐labeled dendrites and cell bodies showed immunolabeling for the μOr. In conclusion, our results indicate that individual neurons in the rat dorsolateral striatum may be directly modulated by both dopaminergic and opioid ligands. These data also suggest that the molecular mechanism responsible for the up‐regulation of μOrs in the caudate and putamen following cocaine exposure may depend, in part, on the co‐existence of D2rs and μ‐Ors in these cells. © 2004 Wiley‐Liss, Inc.