Subcellular distribution of 5-hydroxytryptamine2A and N-methyl-D-aspartate receptors within single neurons in rat motor and limbic striatum.

The dorsolateral caudate-putamen nucleus (CPN) and the nucleus accumbens (NAc) shell, respectively, are involved in many motor and limbic functions that are affected by activation of the 5-hydroxytryptamine2A receptor (5HT2AR) and the N-methyl-D-aspartate subtype of glutamate receptor (NMDAR). We examined the functional sites for 5HT2AR activation and potential interactions involving the NMDAR subunit NR1 (NMDAR1) within these striatal regions. For this examination, sequence-specific antipeptide antisera against these receptors were localized by electron microscopic dual-labeling immunocytochemistry in the rat brain. In the dorsolateral CPN and the NAc shell, the 5HT2AR-labeled profiles were mainly dendrites, but somata and axons were also immunoreactive. The neuronal somata contained round unindented nuclei that are typical of spiny striatal neurons, although few dendritic spines were 5HT2AR immunolabeled. In all neuronal profiles, the 5HT2AR labeling was primarily associated with cytoplasmic organelles and more rarely was localized to synaptic or nonsynaptic plasma membranes. Colocalization of 5HT2AR and NMDAR1 was seen primarily in somata and dendrites. Significantly greter numbers of 5HT2AR- or 5HT2AR- and NMDAR1-containing dendrites were seen in the dorsolateral CPN than in the NAc shell. As compared with 5HT2AR, NMDAR1 labeling was more often observed in dendritic spines, and these were also more numerous in the CPN. These results indicate that 5HT2A and NMDA receptors are coexpressed but differentially targeted in single spiny striatal neurons and are likely to play a major role in control of motor functions involving the dorsolateral CPN.