Ultrastructural relationship between N-methyl-d-aspartate-NR1 receptor subunit and mu-opioid receptor in the mouse central nucleus of the amygdala

The central nucleus of the amygdala (CeA) is an important neuroanatomical substrate of emotional processes that are critically involved in addictive behaviors. Glutamate and opioid systems in the CeA play significant roles in neural plasticity and addictive processes, however the cellular sites of interaction between agonists of N-methyl-d-aspartate (NMDA) and μ-opioid receptors (μOR) in the CeA are unknown. Dual labeling immunocytochemistry was used to determine the ultrastructural relationship between the essential NMDA-NR1 receptor subunit and μOR in the CeA. It was found that over 80% of NR1-labeled profiles were dendrites while less than 10% were axons. In the case of μOR-labeled profiles, approximately 60% were dendritic, and over 35% were axons. Despite their somewhat distinctive patterns of cellular location, numerous dual-labeled profiles were observed. Approximately 80% of these were dendritic, and less than 10% were axonal. Moreover, many dual-labeled dendritic profiles were contacted by axon terminals receiving asymmetric-type synapses indicative of excitatory signaling. These results indicate that NMDA and μORs are strategically localized in dendrites, including those receiving excitatory synapses, of central amygdala neurons. Thus, postsynaptic co-modulation of central amygdala neurons may be a key cellular substrate mediating glutamate and opioid interaction on neural signaling and plasticity associated with normal and pathological emotional processes associated with addictive behaviors.