Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates bidirectional, sodium-independent transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine. OCT3-mediated transport is directly inhibited by corticosterone, suggesting a potential role for the transporter in mediating some of the effects of stress and glucocorticoids on monoaminergic neurotransmission. To elucidate the importance of OCT3 in clearance of extracellular monoamines in the brain, we used immunohistochemical techniques to describe the distribution of OCT3-like-immunoreactive (OCT3-ir) cells throughout the rostrocaudal extent of adult male rat brains. OCT3-ir cell bodies were widely distributed throughout the brain, with the highest densities observed in the superior and inferior colliculi, islands of Calleja, subiculum, lateral septum, lateral and dorsomedial hypothalamic nuclei, and granule cell layers of the main and accessory olfactory bulbs, the cerebellum, and the retrosplenial granular cortex. OCT3-ir cells and/or fibers were also observed in circumventricular organs, and OCT3-ir ependymal cells were observed in the linings of all cerebral ventricles. The widespread distribution of OCT3-ir cell bodies, including regions receiving dense monoaminergic projections, suggests an important role for this transporter in regulating extracellular concentrations of monoamines in the rat brain and is consistent with the hypothesis that corticosterone-induced inhibition of OCT3-mediated transport may contribute to effects of acute stress or corticosterone on monoaminergic neurotransmission.