Cellular sites for activation of delta-opioid receptors in the rat nucleus accumbens shell: relationship with Met5-enkephalin.

The shell compartment of the nucleus accumbens (AcbSh) is prominently involved in the rewarding aspects of delta-opioid receptor (DOR) agonists, including one of its putative endogenous ligands, Met5-enkephalin (Enk). We examined the ultrastructural immunocytochemical localization of an antipeptide DOR antiserum and an antibody against Enk to determine the major cellular sites for DOR activation and the spatial relationship between DOR and Enk in this region. Sixty percent of DOR-immunoreactive profiles were axon terminals and small unmyelinated axons, whereas the remainder were mainly dendrites and dendritic spines. In axons and terminals, DOR labeling was distributed along plasma and vesicular membranes. DOR-containing terminals were mainly large and primarily formed symmetric synapses or occasionally asymmetric synapses. DOR immunoreactivity also was associated with terminals that were small and formed punctate symmetric or nonrecognizable synapses. Dual immunoperoxidase and immunogold labeling showed that 35% of DOR-labeled axons apposed other terminals that contained Enk. In addition, 25% of the DOR-labeled terminals contained Enk. Thirty-five percent of DOR labeling was observed within dendrites and dendritic spines. DOR-labeled spines showed intense immunoreactivity within asymmetric postsynaptic junctions, which were formed by terminals that lacked Enk immunoreactivity. DOR-labeled spines, however, were apposed to Enk-containing terminals in 13% of all associations between dually labeled profiles. These results provide ultrastructural evidence that activation of DOR in the AcbSh is primarily involved in modulating the presynaptic release of mainly inhibitory, but also excitatory, neurotransmitters. These data also suggest that DOR plays a role in determining the postsynaptic response to excitatory afferents.