The behavioral effects of psychostimulants, which are produced at least in part through inhibition of the dopamine transporter (DAT), are modulated by kappa-opioid receptors (KOR) in the nucleus accumbens (Acb). Using electron microscopic immunocytochemistry, we reveal that in the Acb KOR labeling is mainly, and DAT immunoreactivity is exclusively, presynaptic. From 400 KOR-labeled presynaptic structures, including axon terminals, intervaricosities, and small axons, 51% expressed DAT and 29% contacted another population of terminals exclusively labeled for DAT. Within axonal profiles that contained both antigens, DAT and KOR were prominently localized to plasma membrane segments that showed overlapping distributions of the respective immunogold-silver and immunoperoxidase markers. KOR labeling was also localized to membranes of small synaptic vesicles in terminals with or without DAT immunoreactivity. In addition, from 24 KOR-immunoreactive dendritic spines 42% received convergent input from DAT-containing varicosities and unlabeled terminals forming asymmetric, excitatory-type synapses. Our results provide the first ultrastructural evidence that in the Acb, KOR is localized to strategic sites for involvement in the direct presynaptic release and/or reuptake of dopamine. These data also suggest a role for KOR in the presynaptic modulation of other neurotransmitters and in the postsynaptic excitatory responses of single spiny neurons in the Acb. Dual actions on dopamine terminals and their targets in the Acb may account for KOR-mediated attenuation of drug reinforcement and sensitization.
Copyright 2001 Wiley-Liss, Inc.