Localization of the delta-opioid receptor and dopamine transporter in the nucleus accumbens shell: Implications for opiate and psychostimulant cross-sensitization

Opiate- and psychostimulant-induced modulation of dopamine transmission in the nucleus accumbens shell (AcbSh) is thought to play a key role in their potent reinforcing and locomotor effects. To investigate the cellular basis for potential functional interactions involving opiates active at the delt a-opioid receptor (DOR) and psychostimulants that bind selectively to the d opamine transporter (DAT), we examined the electron microscopic localizatio n of their respective antisera in rat AcbSh. DOR immunoperoxidase labeling was seen primarily, and DAT immunogold particles exclusively, in axon termi nals. In these terminals, DOR immunoreactivity was prominently associated w ith discrete segments of the plasma membrane and the membranes of nearby sm all synaptic and large dense core vesicles. DAT immunogold particles were a lmost exclusively distributed along nonsynaptic axonal plasma membranes. Th irty-nine percent DOR-labeled profiles (221/566) either apposed DAT-immunor eactive terminals or also contained DAT Of these 221 DOR-labeled profiles, 13% were axon terminals containing DAT and 15% were dendritic spines appose d to DAT-immunoreactive terminals. In contrast, 70% were morphologically he terogeneous axon terminals and small axons apposed to DAT-immunoreactive te rminals. Our results indicate that DOR agonists in the AcbSh can directly m odulate the release of dopamine, as well as postsynaptic responses in spiny neurons that receive dopaminergic input, but act principally to control th e presynaptic secretion of other neurotransmitters whose release may influe nce or be influenced by extracellular dopamine. Thus, while opiates and psy chostimulants mainly have differential sites of action, cross-sensitization of their addictive properties may occur through common neuronal targets. ( C) 1999 Wiley-Liss, Inc.