Mu-opioid and NMDA-type glutamate receptors are often colocalized in spiny neurons within patches of the caudate-putamen nucleus.

The patch compartments of the caudate-putamen nucleus (CPN) are enriched in mu-opioid receptors (MORs) and have been recently implicated in reward-related behaviors. This function has been established more clearly in the nucleus accumbens, where physiological and anatomical studies show reward-associated interactions involving MORs and N-methyl-D-aspartate-type glutamate receptors (NMDARs). We examined the immunolabeling for MOR and NMDAR subunit NR1 in patches of the rat CPN to determine the potential relevance of dual activation of the respective receptors. Electron microscopy showed the presence of MOR and/or NR1 immunoreactivity (IR) in many perikarya, dendrites, and spines and in morphologically heterogeneous axon terminals. In each 1,000-microm(2) area, the dually labeled dendrites and spines constituted 65% (37/57) and 37% (9/25) of the total NR1-labeled and 34% (37/109) and 13% (9/71) of the total MOR-labeled dendritic profiles. Dually labeled spines received asymmetric excitatory-type synapses from terminals, which were generally unlabeled, but also occasionally contained MOR and/or NR1. The asymmetric synapses comprised the majority (81%) of the total 263 synaptic contacts between MOR- and NR1-labeled neuronal profiles. In dendrites and spines, MOR-IR was localized mainly along nonsynaptic plasma membranes, whereas NR1-IR was more often associated with asymmetric postsynaptic densities and cytoplasmic organelles. In contrast to dendrites, 6% (1.3/22) of NR1-IR and 4% (1.3/33) of MOR-IR axon terminals were dually labeled in each 1,000-microm(2) area. Most singly or dually labeled terminals formed asymmetric synapses with MOR- or NR1-labeled spines. Our results suggest that opioids acting through MOR and excitatory neurotransmitters through NMDAR dually regulate the output of single spiny neurons and some of their excitatory afferents in the CPN.