Cellular sites for dynorphin activation of kappa-opioid receptors in the rat nucleus accumbens shell

The nucleus accumbens (Acb) is prominently involved in the aversive behavio ral aspects of kappa-opioid receptor (KOR) agonists, including its endogeno us ligand dynorphin (Dyn). We examined the ultrastructural immunoperoxidase localization of KOR and immunogold labeling of Dyn to determine the major cellular sites for KOR activation in this region. Of 851 KOR-labeled struct ures sampled from a total area of 10,457 mu m(2), 63% were small axons and morphologically heterogenous axon terminals, 31% of which apposed Dyn-label ed terminals or also contained Dyn. Sixty-eight percent of the KOR-containi ng axon terminals formed punctate-symmetric or appositional contacts with u nlabeled dendrites and spines, many of which received convergent input from terminals that formed asymmetric synapses. Excitatory-type terminals that formed asymmetric synapses with dendritic spines comprised 21% of the KOR-i mmunoreactive profiles. Dendritic spines within the neuropil were the major nonaxonal structures that contained KOR immunoreactivity. These spines als o received excitatory-type synapses from unlabeled terminals and were appos ed by Dyn-containing terminals. These results provide ultrastructural evide nce that in the Acb shell (AcbSh), KOR agonists play a primary role in regu lating the presynaptic release of Dyn and other neuromodulators that influe nce the output of spiny neurons via changes in the presynaptic release of o r the postsynaptic responses to excitatory amino acids. The cellular distri bution of KOR complements those described previously for the reward-associa ted mu- and delta-opioid receptors in the Acb shell.