Major coexpression of kappa-opioid receptors and the dopamine transporter in nucleus accumbens axonal profiles

The behavioral effects of psychostimulants, which are produced at least in part through inhibition of the dopamine transporter (DAT), are modulated by K-opioid receptors (KOR) in the nucleus accumbens (Acb). Using electron mi croscopic immunocytochemistry, we reveal that in the Acb KOR labeling is ma inly, and DAT immunoreactivity is exclusively, presynaptic. From 400 KOR-la beled 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 containe d 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 me mbranes of small synaptic vesicles in terminals with or without DAT immunor eactivity. In addition, from 24 KOR-immunoreactive dendritic spines 42% rec eived convergent input from DAT-containing varicosities and unlabeled termi nals forming asymmetric, excitatory-type synapses. Our results provide the first ultrastructural evidence that in the Acb, KOR is localized to strateg ic sites for involvement in the direct presynaptic release and/or reuptake of dopamine. These data also suggest a role for KOR in the presynaptic modu lation of other neurotransmitters and in the postsynaptic excitatory respon ses 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 dr ug reinforcement and sensitization. (C) 2001 Wiley-Liss, Inc.