Ultrastructural localization of the serotonin transporter in limbic and motor compartments of the nucleus accumbens

Extracellular levels of serotonin [5-hydroxytryptamine (5-HT)] in the nucle us accumbens (NAc) can influence both cognitive and motor functions involvi ng extensive connections with the frontal cortex. The 5-HT levels reflect v esicular release and plasmalemmal reuptake through the serotonin transporte r (SERT). We used electron microscopic immunocytochemistry to determine the sites for SERT activation in the limbic shell and motor-associated core of the rat NAc. Of the SERT-immunoreactive profiles in each region,>90% were serotonergic axons and axon terminals; the remainder were nonserotonergic d endrites and glia. Axonal SERT immunogold labeling was seen mainly at nonsy naptic sites on plasma membranes and often near 5-HT-containing large dense core vesicles (DCVs). SERT-labeled axonal profiles were larger and had a h igher numerical density in the shell versus the core but showed no regional differences in their content of SERT immunogold particles. In contrast, im munoreactive dendrites had a lower numerical density in the shell than in t he core. SERT labeling in dendrites was localized to segments of plasma mem brane near synaptic contacts from unlabeled terminals and/or dendritic appo sitions. Our results suggest that in the NAc (1) reuptake into serotonergic axons is most efficient after exocytotic release from DCVs, and (2) increa sed 5-HT release without concomitant increase in SERT expression in individ ual axons may contribute to higher extracellular levels of serotonin in the shell versus the core. These findings also indicate that SERT may play a m inor substrate-dependent role in serotonin uptake or channel activity in se lective nonserotonergic neurons and glia in the NAc.