Ultrastructural localization and comparative distribution of nitric oxide synthase and N-methyl-D-aspartate receptors in the shell of the rat nucleus accumbens

Nitric oxide (NO), the diffusible gas formed by nitric oxide synthase (NOS) has been implicated in the enhanced locomotor activity attributed mainly to increased dopamine release in the shell of the nucleus accumbens (Acb). Furthermore, the release of both NO and dopamine are known to be altered by agonists of N-methyl-D-aspartate (NMDA) type glutamate receptors in this region. We examined the cellular sites of NO synthesis and the sites of potential relevancy for functional associations between neurons containing NOS and the NMDA receptor in the shell of the Acb. This was achieved by dual ultrastructural immunogold and immunoperoxidase labeling of antisera raised against the brain form of NOS and the NMDAR1 subunit of the NMDA receptor in this region of rat brain. NOS-like immunoreactivity (NOS-LI) was seen throughout the cytoplasm of isolated medium-large somata, aspiny dendrites and axon terminals. In 217 NOS-labeled profiles, NMDAR1-like immunoreactivity (NMDAR1-LI) was colocalized in 17% of somata and dendrites. Additionally, 35% of NOS-labeled dendrites apposed glial processes containing NMDAR1-LI, and 29% apposed axon terminals containing NMDAR1-LI. NOS-labeled terminals more rarely colocalized NMDAR1 or apposed NMDAR1-labeled glial processes or dendrites. These results provide anatomical evidence that, in the shell of the Acb, NMDA receptors are localized so as to directly modulate the output of neurons producing NO as well as to influence other neurons and glia having the greatest access to the released gas.