Presynaptic dopamine D-4 receptor localization in the rat nucleus accumbens shell

Dopamine D-4 receptors in the nucleus accumbens shell (AcbSh) are thought t o play a key role in mediating the locomotor and sensitizing affects of psy chostimulants, as well as the therapeutic efficacy of atypical antipsychoti c drugs. We used electron microscopic immunocytochemistry to determine the functional sites for endogenous and exogenous D-4 receptor activation in th is region. Of 1,090 D-4 receptor-labeled profiles observed in the AcbSh of rat brain, 65% were axons and axon terminals, while 22% were dendrites and dendritic spines. Within axons and terminals, D-4 receptor immunoreactivity was localized to segments of the plasma membrane and membranes of nearby v esicles. The axon terminals were morphologically heterogenous, varying in s ize and content of either all small synaptic vesicles (ssv), or ssv and lar ge dense-core vesicles. The labeled terminals occasionally formed asymmetri c excitatory-type axospinous synapses, but the majority were without recogn izable synaptic specializations. In a separate series of tissue sections th at were processed for dual-labeling of the D-4 receptor and the catecholami ne synthesizing enzyme, tyrosine hydroxylase (TH), 56% of all observed asso ciations were appositions between differentially labeled axonal profiles, a nd 17% were terminals that contained immunoreactivity for both antigens. De ndritic spines containing D-4 receptor-labeling also received convergent in put from TH-immunoreactive terminals and unlabeled terminals forming asymme tric synapses. These results provide the first ultrastructural evidence for a major presynaptic, and a more minor postsynaptic, involvement of D-4 rec eptors in dopaminergic modulation of excitatory transmission in the AcbSh. (C) 2000 Wiley-Liss, Inc.